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Prospect of
Human Age Reversal
William Faloon
RAADFest
October 2nd, 2021
age-reversal.net
This entire presentation available at:
 Biomedical research findings since last year's RAADfest.
 What people can do now to live 5 more years.
 Repopulate bone marrow with autologous induced
hematopoietic stem cells to reverse immune senescence.
 Transhumanist advances over last few months.
Transcending Towards Immortality
Today’s overview…
Life Extension® was born in
January 1977
 Life Extension® incorporated in 1977 in Florida.
 First published in 1980. (Anti-Aging News)
 World’s largest anti-aging organization…over 400,000 supporters. (2021)
Life Extension Center-Pompano Beach, Florida (1977)
Reduce Bone
Facture Risks
1980-1986-Anti-Aging News
1986-1994-Life Extension Report
1994-2021-Life Extension Magazine
41 Consecutive Years
of Monthly Publication
(419,000 copies mailed last month)
Our Controversial Contention
It may be possible…
To Reverse Aging in Humans Today
www.age-reversal.net
“In the Search to Stall Aging, Biotech Startups Are Out
for Blood”
May 13, 2021
https://www.smithsonianmag.com/innovation/in-search-to-stall-aging-biotech-startups-are-out-for-blood-180977728/
Mixing young and old blood flows
Black Circles = Rats Given Young Plasma --- White Circles = Control Rats
Young Plasma Treated Rats Live Healthier and Longer Than Control Group
Young Plasma Group
Control Group
AGE: 31.8 months
Control (left)
Young plasma (right)
CONTROL
AGE: 31.8 months
1 control
3 young plasma
TREATED TREATED
CONTROL
AGE: 34.5 months
AGE: 34.5 Months: Two Young Plasma Treated Rats and Control in Middle
TREATED TREATED
CONTROL
Survival + Quality of Life Improvements in rats receiving Young Plasma (i.p.) every 2 weeks
Control Group
At 29 months untreated rats
start rapid Die Off
u
Treatment Group
Rats aged human equivalent of 60
years given Young Plasma via
Intraperitoneal injection.
Transient improvement in quality of life.
Average Lifespan of untreated group:
29.8 months (70 years in humans)
Average Lifespan of Treated group:
32 months (77 years in humans)
On May 23, 2021, seven treated rats
alive compared to one living control.
On July 20, 2021, two treated rats alive
compared to one living control.
Email from Professor Rodolfo Goya to Bill Faloon- August 16th, 2021
Plasma Treated Rats Start Die Off at 31 months
Age (months)
34
27 28 33
32
31
29 30
26
25 34
Conclusions:
Young plasma seems to possess
revitalizing factors able to
remarkably improve the quality of
life of old rats and moderately
extends their lifespan.
DNA methylation controls the
transcription (activation) of genes.
Without proper DNAmethylation,
beneficial genes are deactivated while
harmful genes can be over-expressed.
DNA Methylation measures Epigenetic Age
Young plasma treatment more than halved epigenetic ages.
This is the principal of what is called
“epigenetic aging.”
Horvath,S.,Singh,K.,Raj,K.,Khairnar,S.,Sanghavi,A.,Shrivastava,A.,...&Lehmann,M.(2020),. Reversing age: dual species measurement of epigenetic age with a single clock. bioRxiv
How to Transition Young Plasma Benefits into Old Humans?
Bone Marrow Yields Regenerative Stem Cells
Bone Marrow
Stem Cell
Niche
Bone Marrow Cell Production
Essential to Sustain Life
Hematopoietic
Stem Cells
Mesenchymal
Stem Cells
+
Stem Cells Naturally Enable Systemic Rejuvenation
But our supply of hematopoietic
and mesenchymal stem cells is
limited.
Transcription Factors can
reprogram old cells into
induced pluripotent stem
cells that can theoretically
regenerate our tissues forever.
Transcription factors turn our genes
“on” and “off ”...so, they are expressed in
the right cell, at the right time, and in the
right amount.
The Nobel Prize in Physiology or Medicine 2012
John B. Gurdon and Shinya Yamana
“For the discovery that mature
cells
can be reprogrammed to become
pluripotent.”
The Nobel Prize recognizes two
scientists who discovered that
mature, specialized cells can be
reprogrammed to become
embryonic cells capable of
developing into all tissues of the
Four specific genes encode transcription factors
that can convert somatic cells into pluripotent
stem cells that can propagate indefinitely.
These transcription factors are collectively called:
“Yamanaka Factors”
https://www.nobelprize.org/prizes/medicine/2012/yamanaka/facts/
Hematopoietic Stem Cell
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hematopoietic-stem-cell
Hematopoietic stem cells develop into
all types of blood cells and are found
in peripheral blood and bone marrow.
With age, hematopoietic stem cells
become depleted and contribute to
immune senescence and anemia.
Healthy hematopoietic stem cells
needed to sustain life.
February 2017
https://www.nature.com/articles/ncomms14533
“How blood can be rejuvenated”
 Blood stem cells generate around a thousand billion new blood cells every day.
 The capacity of hematopoietic stem cells to produce new blood cells diminishes with age.
 Older people more susceptible to anemia, lowered immunity, and blood cancers.
 Researchers at Lund University (Sweden) rejuvenate blood stem cells in aged mice.
“We found that there was no difference in blood-generating capacity when we
compared the reprogrammed blood stem cells with healthy blood stem cells from
a young mouse. This is, as far as we know, the first time someone has directly
succeeded in proving that it is possible to recreate the function of young stem
cells from a functionally old cell.”
Transplanting Hematopoietic Stem Cells into Old
Mice Yields Restoration of Blood Cell Production
https://www.nature.com/articles/ncomms14533/figures/1
February 28, 2021
 This 2021 published review and additional investigations
summarize age-reversal impact of cell reprograming.
 Human trials being investigated
 Funded by Bill Faloon and other charitable donors
https://pubmed.ncbi.nlm.nih.gov/33627519
“When cells were reprogrammed with a 6-factor
cocktail the (degenerative) alterations were
fully reversed and cells fully rejuvenated.”
Elderly
Human
Experimental Approach to
Reverse Systemic Aging
Reprogram Old Functional Cells into Autologous Pluripotent Stem Cells
Old Somatic Cells
Remove somatic
(fibroblast) cells
Potential Systemic
Regeneration using
Induced Pluripotent
Stem Cell Therapy
Somatic Cells
Induced
Pluripotent
Stem Cell-based
Therapy
Cellular Reprogramming
adding NANOG + LIN28
Yamanaka Factors
Purification of induced
progenitors to remove
non-differentiated iPSCs
Autologous iPSC
(Induced Pluripotent Stem Cells)
Old fibroblasts reprogrammed into autologous induced pluripotent stem/progenitor cells
iPSC-derived progenitor cells
Step 1: Selectively remove senescent bone marrow cells.
Step 2: Replace with induced autologous pluripotent
hematopoietic stem cells to rebuild immunity.
Step 3: Also use transcription factors to make autologous
mesenchymal stem cells for systemic regeneration.
Rebuild Bone Marrow to Restore Youth
Human Research Initiative:
Large animal pilot studies will first evaluate safety and regenerative efficacy.
“Young bone marrow rejuvenates
aging mouse brains, study finds”
Microglia in brains of old mice have fewer/shorter branches than young mice
Available at: https://medicalxpress.com/news/2019-02-young-bone-marrow-rejuvenates-aging.html.
Feb. 20, 2019
Synaptic branches of microglia of old mice who received bone marrow
transplants from young mice resembled those of young mice
Young bone marrow transplants
restore exploratory activity in old mice
Feb. 20, 2019
“Remarkably, young
bone marrow
recipients, but not
old bone marrow
recipients, were
more active than
old control mice.”
https://www.nature.com/articles/s42003-019-0298-5/figures/1
March 2020
Overall Mortality
Reduced by 58%
Median Lifespan Increased
12% in Aged Mice
“The increase in longevity was accompanied by reductions of
frailty…Our findings have implications for further development
of stem cell therapies for increasing health and lifespan.”
Intervention: Old hematopoietic stem cells replaced with young‐donor hematopoietic stem
cells using novel mobilization‐enabled hematopoietic stem cell transplantation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059148/
May 14, 2021
Four Transcription Factors Increase
Longevity in Whole Animals
Progerin producing mice treated early in life with “transcription factors “had improved tissue
structures in bone, lung, spleen, kidney and skin, with an increased lifespan of 15%, associated
to a differential DNA methylation signature.
Maximum lifespan increased in certain groups
(61 weeks…11 weeks longer than longest lived animals)
“Altogether, our results indicate that a single short reprogramming
early in life might initiate and propagate an epigenetically related
rejuvenated cell physiology, to promote a healthy lifespan.”
https://www.biorxiv.org/content/10.1101/2021.05.13.443979v1
https://www.creative-biolabs.com/stem-cell-therapy/mesenchymal-stem-cells-mscs-differentiation-
services.htm?gclid=CjwKCAjw9aiIBhA1EiwAJ_GTStzlhTD64Q3aZTnBjCMQmkDRggtvmM9G1k0DWD3yZIutOQe6TuLOnxoCLvkQAvD_BwE
Mesenchymal Stem Cells (MSCs) Differentiation Services
A company that offers MSC differentiation services.
Mesenchymal stem cells (MSCs) are
undifferentiated multipotent cells that
possess potential in tissue regeneration and
cell-based therapy due to their multipotency.
Application of MSCs requires their isolation
and direction of their differentiation into the
appropriate lineage.
Creative Biolabs offers customized services
for reliable in vitro induction of MSCs into
osteogenic, adipogenic, muscular, and
chondrogenic lineages.
RestoringImmunityby RebuildingBoneMarrow
https://www.magentatx.com/revolutionizing-medicine/programs/
Fibroblast cells make up extracellular
matrix and collagen.
Cell reprogramming converted old fibroblasts into
induced autologous pluripotent stem cells.
In vivo research seeks to repopulate bone marrow
niche with induced autologous hematopoietic and
mesenchymal stem
cells (from old autologous fibroblasts).
Objective: Reverse immune senescence
and rejuvenate tissues.
Research Project:
In vivo Human Study Using Induced Hematopoietic and
Mesenchymal Stem Cells Derived from Autologous Fibroblasts
Skin Derived Fibroblast Cell r
Yamanaka Factors
Potential Systemic
Regeneration Using
Induced Pluripotent
Stem Cell Therapy
Cellular
(Induced Pluripotent Stem Cells)
Induced
Pluripotent
Stem Cell-based
Therapy
iPSC-derived progenitor cells
Old fibroblasts reprogrammed into autologous induced pluripotent stem/progenitor cells
Cellular Reprogramming
adding NANOG + LIN28
Elderly
Purification of induced
progenitors to remove
non-differentiated iPSCs
Apple News - July 11, 2021
“Can Science Cure Death?
It Sure Looks Like It”
“The World Health Organization added
a distinction that characterizes aging
as a disease.”
https://apple.news/A4LOishZsQQ2xGEgHrlSCxA
“Saraev, like any number of young optimistic
tech-associated men believes that if he takes
the correct preventative steps now, he might
well live forever.”
Changing Manufacturing Forever
October 17th 2020
“This Japanese Engineer Created the Robots That Make Your
Created $40 Billion Company
Dies in 2020 at age 95
Mr. Inaba read a 1952 article in
Scientific American describing
rudimentary computer program that
told a machine how to carve up a
piece of metal.
He advanced this early MIT technology
into “programmable machine tools”
that enable today’s computer-driven
assembly lines.
https://www.wsj.com/articles/this-japanese-engineer-created-the-robots-that-make-your-cars-11602856803
Genesis of this Breakthrough was year 1952 Scientific American article!
https://www.scientificamerican.com/article/aging-is-reversible-at-least-in-human-cells-and-live-mice/
“New research suggests it is possible to slow or even reverse aging,
at least in mice, by undoing changes in gene activity—the same
kinds of changes that are caused by decades of life in humans.”
What’s Transpired Since RAADfest 2020?
October 2nd - 4th 2020
Sept 30, 2020
British billionaire Jim Mellon plans to take his
life extension start-up public in six to 12 months
“Juvenescence has raised about $170 million
privately and still has a “fair amount of money
left in the bank.”
“Mellon isn’t the only billionaire who wants to
live beyond a hundred.
Michael Bloomberg, told Business Insider in
2017 he wants to live until he’s 125.”
https://www.cnbc.com/2020/09/29/billionaire-jim-mellon-plans-to-take-life-extension-start-up-public.html#:~:text=LONDON%20%E2%80%93%20British%20billionaire%20Jim%20Mellon,to%20extend%20the%20human%20life.
Jim Mellon
Born: February 1957
“Plasma dilution improves cognition and
attenuates neuroinflammation in old mice”
“Explaining the mechanism of the positive effects of
neutral blood exchange on the brain, our
comparative proteomics analysis demonstrated that
dilution of old blood plasma yields an increase in the
determinants of brain maintenance and repair in
mice and in people.
These findings confirm the paradigm of rejuvenation
through dilution of age-elevated systemic factors
and extrapolate it to brain health and function.”
https://link.springer.com/article/10.1007/s11357-020-00297-8
November 15, 2020
https://medicalxpress.com/news/2020-11-hyperbaric-oxygen-treatments-reverse-aging.html
“Study finds hyperbaric oxygen treatments reverse aging process”
A new study from Tel Aviv University and the
Shamir Medical Center in Israel indicates that
hyperbaric oxygen treatments in healthy aging
adults can stop the aging of blood cells and
reverse the aging process.
In the biological sense, the adults' blood cells
actually grow younger as the treatments
progress.
November 20, 2020
v
Tel Aviv University
Research Paper
Hyperbaric oxygen therapy increases telomere length
and decreases immunosenescence in isolated blood
cells: a prospective trial
Yafit Hachmo1, * , Amir Hadanny2,3,4, * , Ramzia Abu Hamed1 , Malka Daniel-
Kotovsky2 , Merav Catalogna2 , Gregory Fishlev2 , Erez Lang2 , Nir Polak2 , Keren Doenyas2 , Mony Fri
edman2 , Yonatan Zemel2 , Yair Bechor2 , Shai Efrati1,2,3,5
•1 Research and Development Unit, Shamir Medical Center, Zerifin, Israel
•2 The Sagol Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center,
Zerifin, Israel
•3 Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
•4 Bar Ilan University, Ramat-Gan, Israel
•5 Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel
* Equal contribution
https://www.aging-us.com/article/202188/text
AgING November 18, 2020
November 19, 2020
“It Sure Looks Like Humans Have Found a Way to Reverse Aging”
https://www.popularmechanics.com/science/health/a34730692/study-reverse-aging-in-humans/
“A landmark study shows the reversal of
biological aging in humans.”
“The researchers used oxygen therapy in a
pressurized chamber to reverse aging in two
key biological clocks.”
“The study showed lengthening in the
telomeres of chromosomes and a decrease in
(senescent) cells known to cause aging.”
Novel Hyperbaric Oxygen Protocol Extends
Telomere Length and Improves Immune Markers
Some immune cell telomeres
elongated by 20%.
Some senescent immune cells
reduced by 37%.
Improved immune markers.
https://www.aging-us.com/article/202188/text
“Human ageing process biologically reversed in world first”
1, https://www.telegraph.co.uk/news/2020/11/18/human-ageing-process-biologically-reversed-world-
first/#:~:text=The%20ageing%20process%20has%20been,that%20comes%20with%20growing%20older
November 18, 2020
“The aging process has been biologically
reversed for the first time by giving humans
oxygen therapy in a pressurized chamber.”
1, https://www.telegraph.co.uk/news/2020/11/18/human-ageing-process-biologically-reversed-world-
first/#:~:text=The%20ageing%20process%20has%20been,that%20comes%20with%20growing%20older
November 18, 2020
“Scientists said the growth may mean
that the telomeres of trial participants
were now as long as they had been
25 years earlier.”
Aviv Clinic
The Villages, FL 32163
https://aviv-clinics.com/hyperbaric-centers/villages-florida/
First Hyperbaric Chamber Clinic of its Type Opens in Central Florida
Total cost is $45,000 broken down into two installments:
- $15,000 to initiate 3 days of evaluations including
advanced brain imaging, cardiopulmonary testing,
diagnostic and functional assessments.
- $30,000 to begin a 3-month, multi-modality treatment
regimen with hyperbaric oxygen, including post treatment
and monitoring.
Aviv Clinics
Center for Advanced Healthcare
2955 Brownwood Blvd., Suite 100
The Villages, FL 32163
Downside: Need to be physically near Central Florida
Hyperbaric Treatment Protocol
 Five daily sessions a week for 3 months
 Each session involved breathing 100%
oxygen by mask for 90 minutes with 5-
minute air breaks every 20 minutes.
 Each total session time about 2 hours.
 Commercial price for 60 sessions:
$18,000
https://www.aging-us.com/article/202188/text
House of
Optimal Health
- Hormones - Kidney function
- LDL/HDL - Vitamin D
- Blood Pressure - Glucose
- C-reactive protein - Homocysteine
- Insulin - Coagulation
Level 2
Level 1
- Senolytics
- NAD+ Restoration
- mTOR-inhibition
- Exosomes
- Stem Cells - Hyperbaric Oxygen
- Young Plasma
Failure to optimize
Level 1, preclude
benefits of Level 2.
Age Reversal Interventions
Healthy Aging
- Perinatal Tissues
December 1, 2020
“Drug reverses age-related cognitive decline within days”
DOI: 10.7554/eLife.62048
UC San Francisco scientists show a few doses of
new small-molecule integrated stress inhibitor:
 Rapid restoration of cognitive function in aged mice
 Reverse cognitive impairments in Down Syndrome
 Restore memory function after traumatic brain injury
 Prevent noise-related hearing loss
 Immune cell rejuvenation
 Enhanced cognition in healthy mice
https://medicalxpress.com/news/2020-12-drug-reverses-age-related-cognitive-decline.html
“Just a few doses of an experimental drug can reverse age-
related declines in memory and mental flexibility in mice”
December 3, 2020
https://www.nature.com/nature/volumes/588/issues/7836
“Reprogramming retinal cells can
reverse age-related vision loss”
 Harvard researchers use three Yamanaka transcription
factors to reprogram retina cells to a more youthful
epigenetic state.
 The transcription factors restored youthful DNA
methylation patterns.
 Old mice with damaged optic nerves grew new axons
and reversed vision loss in this model of glaucoma.
“These results show that mammalian tissues retain a record of
youthful information, encoded in part by DNA methylation,
which can be accessed to improve tissue function and
potentially to reverse the effects of aging.”
Nature 588, 34-36 (2020doi: https://doi.org/10.1038/d41586-020-03119-1)
Restoring Vision in Mice via Axon
Regeneration
natur
e
December 2, 2020
Restoring vision in mice. Retinal ganglion cells (RGCs) transmit visual information from the eye to the brain
along projections called axons. Damage to the RGC axons prevents transmission of this information, leading to
sight loss. Lu et al.2 report that treatment of damaged RGCs with a transcription-factor cocktail called OSK
restores the cells to a youthful state, leading to axon regeneration and restoration of sight in mice.
December 30, 2020
https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/
“Cracking the code of biological aging
could solve America’s health care crisis”
“The most exciting opportunity
for such an improvement in
health productivity is to
understand and address the
biology of aging.”
Dec. 30, 2020
 Therapeutic Plasma Exchange---Conboy Lab-UCBerkeley
 Thymic Regeneration---Greg Fahy-InterveneImmune
 Reverse extra-cellular protein stiffening (glycation)
Age-Reversal Interventions Highlighted:
https://www.sciencedirect.com/science/article/pii/S1568163720302324
https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/
“With such treatments, Americans would
experiencemorehealthy,productiveyearsoflife.”
“Withouttreatmentstosloworreverse aspects
of biologicalaging,anagingpopulationmeans
we areinfor ahealthcarecosttsunami.”
Dec. 30, 2020
https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/
Mainstream Recognition of
The Need to Reverse Human Aging
“…why not launch an
Operation Warp Speed
for biological aging?”
CONCLUSION
https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/
December 30, 2020
Scientists have identified synergistic cellular pathways for
longevity that amplify lifespan fivefold in C. elegans, a
nematode worm used as a model in aging research.
“The increase in lifespan would be the
equivalent of a human living for 400 or 500
years, according to one of the scientists.”
Jianfeng Lan, Jarod A. Rollins, Xiao Zang, Di Wu, Lina Zou, Zi Wang, Chang Ye, Zixing Wu, Pankaj Kapahi, Aric N. Rogers, Di
Chen. Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity. Cell Reports, 2019;
28 (4): 1050 DOI: 10.1016/j.celrep.2019.06.078
“Pathways that extend lifespan
By 500 percent identified” Jan 8, 2020
“In fact, the two pathways which the team
manipulated—known as the insulin signaling
and TOR pathways—are also found in people.
SCIENTISTS EXTENDED THE LIFESPAN
OF THESE ANIMALS BY 500 PERCENT
Jan 9, 2020
https://www.newsweek.com/scientists-extend-lifespan-animals-500-percent-1481241
This means that the latest results could
have implications for the development
of new anti-aging therapies.”
Age Reversal
Interventions
Autophagy Inflammation
Remove
senescent cells
Restore
youthful methylation
Lengthen
telomeres
AMPK/
mTOR
Sirtuins/
NAD+
Exosomes
Hyperbaric
https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
“…mice with progeria that got the
gene-editing treatment lived more than
twice as long as the untreated mice.”
CRISPR Gene-Editing Treatment
Jan7,2021
CRISPR-Treated Progeroid Mouse
17 Months
>160 Years?
7.1 Months
Combination CRISPR-Treated Human
Untreated Progeroid Mouse
https://www.nature.com/articles/s41586-020-03086-7 https://doi.org/10.1073/pnas.1910073116
Extrapolation Assuming
Multi-Gene Edits in Normal
Aged People via CRISPR
1) 25% extended lifespan in normal aged mice.1
2) Improved overall appearance and grip strength.1
“A genome-wide CRISPR-based screen identifies
KAT7 as a driver of cellular senescence”
January 6, 2021
1. https://stm.sciencemag.org/content/13/575/eabd2655/tab-pdf
2. https://www.genome.gov/10001345/importance-of-mouse-genome
Mice and humans share virtually the same set of genes though in slightly different forms.2
KAT7 gene is significant driver of cell senescence. Targeting KAT7 using CRISPR enabled:
98-Year Average Lifespan?
25% Lifespan Extension
It May Be Possible for Normal Aged People to
Benefit from these Kinds of Single-Gene CRISPR Edit
If this CRISPR-Treatment Works Similar in Normal Aged Humans
CRISPR-Treated NormalAged Mouse
Science Translational Medicine. 06 Jan 2021:Vol. 13, Issue 575, eabd2655. DOI: 10.1126/scitranslmed.abd2655
https://www.dailymail.co.uk/sciencetech/article-9166007/Chinese-scientists-develop-gene-therapy-delay-ageing.html
Mainstream News Coverage
of CRISPR Longevity Study
January 21, 2021
“A new gene therapy has
been shown to reverse
some of the effects of
aging in mice and
extend their lifespans by
up to a quarter.”
Covid shows that aging is like a disease
—we should treat it accordingly
January 22, 2021
 “Covid-19 may be a disease of aging, as well as a respiratory illness.
 … some anti-aging therapies could prove as important in the 21st century
as antibiotics were in the 20th.
 The pandemic has left people more frightened than ever about getting
old…it has also left clues that could prompt a revolution in how we think
about aging.”
https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging
“Fueled in part by a billion dollars of
investor money, they are attempting
to reverse-engineer your molecular
biological clock.
Their goal?
To eliminate not merely diseases that
kill people, but to prevent death
itself.”
Feb 20, 2021
Is There a Cure for Aging?
https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging
Feb. 20, 2021
“the immortal jellyfish...cheats death
by reverting from adulthood back to
its polyp stage when threatened with
danger or starvation.”
“and lobsters' stock a seemingly
limitless supply of a youthful enzyme
that has some scientists wondering if
the crustacean, under the best
conditions, just might live forever.”
“…the immortal
jellyfish”
(Turritopsis
dohrnii)
February 10, 2021
February 20, 2021
“I don’t see why eliminating a
disability or giving a kid blue
eyes or adding 15 IQ points is
truly a threat to public health or
to morality,” says the Harvard
gene-editing pioneer George
“The new biotechnology called
CRISPR offers the prospect of
defeating lethal viruses and curing
genetic diseases, even as it raises
serious moral questions.”
C = Clustered
R = Regularly
I = Interspaced
S = Short
P = Palindromic
R = Repeats
CRISPR is a family of DNA sequences found in
genomes of prokaryotic organisms such as bacteria
CRISPR Gene-Editing Treatment
An untreated progeria mouse at 7.5
months of age, with a thin, grayish
coat, pronounced spinal curvature,
and low activity levels. Untreated
progeria mice have an average
lifespan of 7.1 months.
Three treated progeria mice at 11
months of age, with healthy
coats, no apparent spinal
curvature, and normal activity
levels. The treated progeria mice
had an average lifespan of 17
months.
CRISPR-Edited
Progeroid Mice
Unedited
Rapid-Aged
Mouse
https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
CRISPR Therapy Corrects Pathologic Mutations in DNA Genes
Healthy Longevity Conferred by Replacing Progeroid DNA
base pair T and A with Normal C and G DNA base pair
https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
1. A ‘base editor’ was designed to home
in on this mutation and correct it to the
normal sequence. The molecule was put
into a special inactivated virus.
How this Gene
Editing Therapy
Extended Life
https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
CRISPR Gene-Editing Treatment
“Could Point Way to Fix for Deadly Aging Disease”
Jan. 7, 2021
Untreated Progeroid Mouse
CRISPR-Treated Progeroid Mouse
7.1 months
17 months
Combination CRISPR-Treated Human
> 160 Years?
https://www.nature.com/articles/s41586-020-03086-7
https://doi.org/10.1073/pnas.1910073116
Extrapolation Assuming Multi-Gene Edits
in Normal Aged People via CRISPR
Results from single dose combination gene therapy:
Noah Davidsohn, Matthew Pezone, Andyna Vernet, Amanda Graveline, Daniel Oliver, Shimyn Slomovic, Sukanya
Punthambaker, Xiaoming Sun, Ronglih Liao, Joseph V. Bonventre, and View ORCID Profile George M. Church
PNAS November 19, 2019 116 (47) 23505-23511; https://doi.org/10.1073/pnas.1910073116
November 19, 2019
1)58%increasedfunctionafterheartfailure
2)38%reductioninvasculardiseasemarker
3) 75% reduction in kidney atrophy
4)Complete reversal ofobesity &diabetes
George Church
https://www.52-insights.com/interview-george-church-playing-god-with-our-genes-science/
May 4, 2018
“We’ve been doing aging reversal
on a variety of different traits —
cardiac disease, kidney, obesity,
diabetes…and we have examples of
gene therapies that can affect all of
these simultaneously.”
“I think we’re talking about
in the next few years seeing
an aging reversal in 12-year-
old dogs.”
newscientist.com/article/mg23931920-600-how-a-positive-mind-really-can-create-a-healthier-body
“George Church: The maverick
geneticist now wants to reverse aging”
DEC. 8, 2019
“A Harvard geneticist's goal: to
protect humans from viruses,
genetic diseases, and aging”
“George Church's lab at Harvard Medical School is
working to make humans immune to all viruses, eliminate
genetic diseases and reverse the aging process…”
March 2, 2021
https://www.sciencealert.com/experimental-crispr-treatment-cuts-cholesterol-in-mice-by-up-to-57-in-single-shot
“In addition to the cholesterol
reduction, the experiment
produced a 29.4% decrease in
triglycerides…”
CRISPR May Eliminate Need for Drugs
Single CRISPR Injection
reduces cholesterol Up
to 57% in Mice
https://www.nytimes.com/2021/03/08/books/review/walter-isaacson-the-code-breaker.html
2020 Nobel Prize in Chemistry
awarded to Jennifer Doudna and
Emmanuelle Charpentier for
CRISPR-cas9 research
“Gene Editing, and the Future of the Human Rac
“The landmark research …has the
potential to control future pandemics
— either by outwitting the next viral
plague through better screening and
treatment or by engineering human
beings with better disease resistance
programmed into their cells.”
March 8 2021
https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging
February 20, 2021
“If the results are what
they think they will be, the
whole world could go on
metformin and extend life
for everybody.”
- Nir Barzilai, lead researcher on
“Targeting Aging with
Clinical Trial”
April 2021
Nov 29, 2015
“Can some drugs delay aging? Scientists focus on tho
that target frailty and age-related disease.”
March 6, 2021
“Leading the list of candidates is metformin, a
longtime treatment for type 2 diabetes, and rapamycin,
a chemotherapy agent and immunosuppressant.
Scientists also are studying a class of compounds
known as senolytics, which attack ‘senescent’ cells in
the body that tend to proliferate with age.”
https://www.washingtonpost.com/health/anti-aging-drugs-metformin-study/2021/03/05/d9de870a-7882-11eb-9537-496158cc5fd9_story.html
FDA has approved a second clinical trial using metformin to target
frailty in people over age 65 in San Antonio area.
Lifestyle Intervention
Plus Metformin to Treat Frailty in
Older Veterans With Obesity
• Third clinical trial receives FDA approval
• Location: Houston, TX
• Status: Recruiting
- Older adults (65 to 85 years)
- Groups:
• Diet-induced weight loss and Exercise Training plus Metformin
• Diet-induced weight loss and Exercise Training plus Placebo
• Healthy lifestyle and Metformin
- Outcome Measures:
• Improvements in physical function, bone mineral density and bone quality, lean body
mass and muscle quality, and markers of senescence-associated phenotype (SASP).
Additional information: https://clinicaltrials.gov/ct2/show/NCT04221750
“Reversal of epigenetic aging and immunosenescent trends in humans.” Aging Cell; Sept 2019
Thymic Age Reversal Demonstrated in 2019
1) Human growth hormone
2) DHEA
3) Metformin
Study conducted by Dr. Greg Fahy in collaboration
with researchers from Stanford University and
UCLA used individualized doses of:
Study subjects also provided with daily
vitamin D3 and zinc.
https:// www.dailymail.co.uk/health/article-7435427/
Oct.22,2019
Turning Back Time!
“Aging is REVERSED in men using a
cocktail of growth hormones and
diabetes drugs in study that saw test
group shed 2.5 biological years.”
Life Extension Magazine
recommended metformin 26
years ago…the FDA went
berserk!
March 1995
Decades of
research reveals
disease-fighting
impact of
metformin.
November 2010
Example of Lethal Delay
https://www.longevity.technology/worlds-first-anti-aging-trial-gets-green-light/
Sept 4, 2019
1958 - Metformin approved as anti-diabetic drug in England
1995 - Life Extension® lists metformin as anti-aging drug
2015 - FDA approves first anti-aging study of a drug (metformin)
2019 - Metformin study receives $75 million funding
($40 million from anonymous donor)
Bridging the Longevity Gap
Urgent Need to Access Age-Reversal Interventions
New CRISPR Technique
Might Edit Epigenetics
• Highly specific DNA methylation
• Does not alter DNA sequence
• Changes DNA methylation
(epigenetic) marks
• Epigenetic changes persist into cell
differentiation to stem cells.
• Might enable altering of cellular
“epigenetic age”
Reference: Nuñez et al. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell. 2021 Apr 7;S0092-8674(21)00353-6.
doi: 10.1016/j.cell.2021.03.025.
April 7, 2021
“An on-off switch for
methylation editing”
Reference: Nuñez et al. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell. 2021 Apr 7;S0092-8674(21)00353-6.
doi: 10.1016/j.cell.2021.03.025.
Control gene expression with
high specificity while leaving
DNA sequence unchanged.
April 7, 2021
 “CRISPR on” can activate target genes with high specificity
 “CRISPR off” can deactivate genes with high specificity
New Technology called “CRISPR 2.0”:
https://www.longevity.technology/michael-greve-commits-e300m-for-rejuvenation-start-ups/
Michael Greve commits €300m for rejuvenation start-
ups
The founder of Forever Healthy has committed
to advance rejuvenation biotech start-ups
With this €300 million ($360 million) commitment,
Greve intends to accelerate the advent of
rejuvenation biotechnology with new, repair-based
approaches that treat the root causes of aging…
Human rejuvenation is not science fiction anymore
and resulting therapies are affordable and
uncomplicated.
May 6, 2021
mTOR Inhibition with rapamycin Improves
Alzheimer’s in Mouse Model of Disease
Effects of rapamycin in mouse model of Alzheimer’s:
Van Skike et al. mTOR attenuation with rapamycin reverses neurovascular uncoupling and memory deficits in mice modeling Alzheimer's disease.
J Neurosci . 2021 Apr 20;JN-RM-2144-20. doi: 10.1523/JNEUROSCI.2144-20.2021. PMID 33888602.
April 20, 2021
•Improved cerebrovascular function
(better than non-Alzheimer’s mice)
•Reduction of beta-amyloid in brain cortex
•Reversed memory deficits
Rapamycin Human Study
Receives $485,000 Funding
 Randomized, placebo-controlled trial into the safety/efficacy of rapamycin in
reducing clinical measures of aging in an older adult population.
 Two differing doses: 5 mg or 10 mg of rapamycin one time a week or placebo.
 Primary Outcome Measure: Changes in visceral fat as measured by (DXA) scan.
 Secondary Outcomes: Range of clinical measures, e.g. bone density, blood tests, etc.
 20 people enrolled at $360 each (original cost before donations was $1,200).
Sponsor: AgelessRx Collaborator: University of California, Los Angeles
Principal investigators: James Watson, M.D. and Sajad Zalzala, M.D.
June 18, 2021
To enroll log on to: https://www.agelessrx.com/pearl
Senolytic Enhances Kidney
Regeneration in Mice
Senolytic treatment with ABT-263:
• Reduced senescent cell numbers
• Restored regenerative profile in
aged mouse kidney
• Improved kidney function2
1. https://www.kidney.org/news/monthly/wkd_aging
2. Mylonas K et al. Cellular senescence inhibits renal regeneration after injury in mice, with senolytic treatment promoting repair. Sci Transl
Med. 2021 May 19;13(594):eabb0203. doi: 10.1126/scitranslmed.abb0203. PMID 34011625.
May 19, 2021
More Than 50% of Americans over age 75 Are Believed to Have Kidney Disease1
June 1, 2021
Buck Institute Announces Non-Invasive
Test to Measure Senolytic Efficacy
Precise measure of senescent cell destruction
demonstrated in cell culture and mice.
USDA funding full time research at Tufts
University to make this available to humans.
Age Reversal Network will assist to develop this
test of senolytic therapy efficacy for upcoming
clinical trials. (September 8, 2021)
When available, this test will enable precise
dosing of senolytic drugs and nutrients.
https://www.cell.com/cell-metabolism/pdf/S1550-4131(21)00115-7.pdf
SIRT6 overexpression extends lifespan in mice
Mice genetically altered to express
more SIRT6 protein showed:
• Median lifespan extension:
27% in males; 15% in females
• Maximum lifespan extension:
11% in males, 15% in females
(Confirms a 2012 study result)
Roichman A. et al. Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nature
Communications. 2021 May 28;12(1):3208. doi: 10.1038/s41467-021-23545-7. PMID 34050173
May 28, 2021
Can we raise SIRT6 now?
• Some fatty acids can increase SIRT6
function1
• Olive & other oleic acid oils1
• Fasting might help1
• Dietary cyanidins in red, purple,
and blue fruits and vegetables
might enhance function2
References
1. Feldman J. et al. Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and
Widespread Deacylation by Mammalian Sirtuins. J Biol Chem. 2013 Oct 25; 288(43): 31350–31356.
doi: 10.1074/jbc.C113.511261. PMID 24052263.
2. Klein M. & Denu J. Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators.
J Biol Chem. 2020 Aug 7; 295(32): 11021–11041. doi: 10.1074/jbc.REV120.011438. PMID 32518153.
https://my.clevelandclinic.org/health/diseases/17855-amyloidosis-attr
What is amyloidosis?
Amyloidosis is a protein misfolding disorder. It causes proteins in the body to change
shape (misfold), bind together and form amyloid deposits that damage tissues.
Transthyretin amyloidosis begins as excess
transthyretin proteins from the liver break
apart and form amyloid fibrils that damage
the heart, nerves and other tissues.
 Transthyretin amyloidosis is caused by the accumulation of misfolded transthyretin proteins.
 Misfolded transthyretin amyloid proteins build up and cause heart failure and other diseases.
 If left untreated death occurs in 2 to 5 years.
CRISPR/Cas9 gene editing reduced serum levels of
transthyretin,
a key biomarker for the disease, by 87% in humans.
(Standard care therapy typically reduces transthyretin by 80%.)
First Human Trial Using CRISPR
June 26, 2021
https://www.fiercebiotech.com/biotech/first-human-trial-results-intellia-shows-world-gene-editing-has-arrived
This is the first-time gene editing has been proven to work in
humans, which “opens up a whole new area of therapies for
patients that wasn't there.”
“The U.S. Military Is Testing a Pill That Could Delay Aging”
• U.S. Special Operations Command
investing more money in anti-aging
clinical trials.
• Trial to start soon of “anti-aging pill”
• NAD+ precursor being tested to enable
“improved human performance…like
increased endurance and faster
recovery from injury.”
July 6th, 2021
https://www.popularmechanics.com/science/health/a36905562/us-military-testing-anti-aging-pill/
“Reduced levels of NAD+ are linked to aging
and numerous diseases, including
mitochondrial dysfunction, inflammation and
a variety of associated diseases. These
levels decline as humans age and remain
depleted during disease states.”
NAD+ Restoration Turned Real 7 Years Ago
• Since 2001, Life Extension®
has sought ways to restore
NAD+.
• NAD+ helps turn “off”
degenerative processes.
• Proven methods to boost NAD+
became available in circa 2014.
November 2014
At age 50, we have 50%
less cell NAD+ than age 20.
By age 80, NAD+ levels
drop as much as 98%.
NAD+ Sharply Plummets with Age
“We show that a slowdown in aging that increases life expectancy
by 1 year is worth US $38 trillion, and by 10 years, US $367 trillion.”
(These estimates are for the United States only.)
July 5, 2021
July 16th 2021
Scientists are demystifying aging —
funding could add decades to our live
BY MATT KAEBERLEIN, OPINION CONTRIBUTOR — 07/16/21 12:01 PM EDT
https://thehill.com/opinion/healthcare/563337-scientists-are-demystifying-aging-funding-could-add-decades-to-our-lives?rl=1
$6.5 billion proposed in Federal funding for “geroscience” research
“Over the past two decades, scientists have learned a great deal about the
biology of aging. At the same time, we are also learning how to tweak those
processes to slow, or even partially reverse, many of the functional declines
that go along with old age.”
September 6, 20181
1. https://www.elevian.com/blog-all/2018/9/15/business-insider-a-harvard-backed-drug-company-is-trying-to-develop-medicine-to-treat-and-prevent-aging-related-diseases
2. https://www.elevian.com/
+ = Bringing GDF11 to Humanity
August 12, 20212
$20 Million additional capital raised + $20 Million more
when First Patient is dosed in Phase 1 Clinical Trial
using recombinant GDF11
Clinical applications of GDF11 in addition
to potential systemic Age Reversal
https://www.elevian.com/#elevian-pipeline
August 21, 2021
Longevity investor Sergey Young is on a mission to extend
people’s healthy lifespans – and knows exactly how it can
be done.
Sergey Young: 'Living to 150 or
200 years old will be as simple as
getting vaccinated today'
“Sergey Young, a venture capitalist who runs
the Longevity Vision Fund, invests in health-
tech companies promising to defeat aging, AI,
Quantum computing, gene editing, the
microbiome and more.”
https://www.telegraph.co.uk/health-fitness/body/would-really-like-live-200/
Long-term treatment with senolytic drugs Dasatinib and
Quercetin ameliorates age-dependent intervertebral disc
degeneration in mice
September 3, 2021
Vertebral disc degeneration is prevalent in
elderly people: leading cause of chronic
back pain and disability.
Systemic administration of dasatinib and
quercetin prevented age-dependent
progression of disk degeneration in mice.
Potential benefits of D + Q treatment include
alleviation of disc degeneration, reduction
in systemic inflammation and improved physical
condition during aging.
https://www.nature.com/articles/s41467-021-25453-2
September 2021
Prevention Magazine
favorably describes:
 Intermittent Fasting
 Metformin
 DNA methylation testing
 Sirtuin activation
 Young plasma transfer
 Senolytic drugs
RAADfest presented these years ago.
(Prevention Magazine initially hostile to anti-aging medicine.)
Rewriting the Rules of Biology
 Time-honored doctrine of biology was that the fate of cells was
irreversibly determined, and that rejuvenation was impossible.
 Starting in 2006, cell reprograming demonstrated cellular rejuvenation.
 Rejuvenation achieved in cells from very old humans (2011).
 Research underway to rejuvenate whole organisms (including humans).
 The “impossible” was achieved overnight via cellular reprograming.
https://pubmed.ncbi.nlm.nih.gov/33627519
Cellular Reprograming
Conveying the Message of Biological Rejuvenation
 Human fate was inescapable: grow old and die!
 Biological rejuvenation called impossible.
 <20 years (blink of eye in evolutionary terms) that fatalistic view became obsolete.
 Technology has turned cell rejuvenation (age-reversal) real.
 In vivo autologous induced pluripotent stem cell research may begin 2022.
Think of how fortunate we are…to live in a time of these
marvelous achievements…a time in which rejuvenation
and indefinite life extension is within our reach.
February 28, 2021
 This 2021 published review and additional investigations
summarize age-reversal impact of cell reprograming.
 Human trials being investigated.
 Funded by Bill Faloon and other charitable donors.
https://pubmed.ncbi.nlm.nih.gov/33627519
“When cells were reprogrammed with a 6-
transcription factor cocktail the (degenerative)
alterations were fully reversed and cells fully
rejuvenated.”
Carnegie Mellon’s Cloud Lab to Automate Labor-Intensive Science Exp
August 31, 2021
• $40 million laboratory designed to automate lab
experiments with robotics and artificial
intelligence.
• Experiments carried out remotely by about 200
different types of AI robotic machines.
• Scientists from around the world can synthesize,
or create, molecules using a robot based in
Switzerland.
“The benefit comes in accelerating science”
https://www.wsj.com/articles/carnegie-mellons-cloud-lab-to-automate-labor-intensive-science-experiments-11630348526?mod=searchresults_pos2&page=1
Sept 4, 2021
“…Silicon Valley’s
latest wild bet on
living forever”
https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/
Sept. 4, 2021
“Meet Altos Labs, Silicon
Valley’s
latest wild bet on living
forever”
https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/
New anti-aging company funded by Jeff Bezos and others to pursue cellular
reprogramming to revitalize entire animal bodies and eventually humans.
Recruiting large cadre of university scientists with lavish salaries and promise they can
pursue unfettered blue-sky research on how cells age and how to reverse that process.
Altos will fund researchers such as Steve Horvath (ULCA inventor of DNA methylation
testing) and Shinya Yamanaka (shared 2012 Nobel Price using “Yamanaka Factors” to
reprogram cells).
September 5, 2021
•The two are funding Altos Labs, which is looking to develop anti-aging techniques
•Among the expertise being brought on include those who have looked extensively
in cell reprogramming
•The technique reverts cells back into their stem cell state, which while dangerous,
can be used to reverse aging
•The technique was first discovered by Dr. Shinya Yamanaka, who will serve as
an advisor to the company
https://www.dailymail.co.uk/news/article-9960175/Jeff-Bezos-Yuri-Milner-fund-anti-aging-start-up.htm
Jeff Bezos and Yuri Milner 'fund anti-aging
start-up aimed at biological reprogramming
which could help humans live FOREVER'
Yamanaka Factors
Potential Systemic
Regeneration using
Induced Pluripotent
Stem Cell Therapy
Cellular
(Induced Pluripotent Stem Cells)
Induced
Pluripotent
Stem Cell-based
Therapy
iPSC-derived progenitor cells
Old fibroblasts reprogrammed into autologous induced pluripotent stem/progenitor cells
Cellular Reprogramming
adding NANOG + LIN28
Elderly
Purification of induced
progenitors to remove
non-differentiated iPSCs
What’s Transpired Since RAADfest 2020?
October 2020 to October 2021
Reaching the Critical Mass: the minimum size or amount
of something required to start or maintain a venture.
Consensus advancing to the “I get it moment” as it relates
to prospect of age reversal.
“Epigenetic rejuvenation seems to hold the key
to arresting or even reversing organismal aging.”
February 28, 2021
FUNDING
The work from our laboratory is supported in part by grants # MRCF 7-25-19 from the
Medical Research Charitable Foundation and the Society for Experimental
Gerontological Research, New Zealand, by a grant from Betterhumans Inc., Florida,
USA and grant #PICT18-00907 from the Argentinian Agency for the Promotion of Science
and Technology to RGG.
https://pubmed.ncbi.nlm.nih.gov/33627519/
“Rejuvenation has already been achieved in old
human and animal cells.
Eight independent studies show that different cell
types from old humans and mice can be
rejuvenated by cell reprogramming.
Achieving the same in humans will be just a matter
of improving our technology.”
Email from Rodolfo Goya, Ph.D. to Bill Faloon - August 5, 2021
Time Restricted Eating
Intermittent Fasting
Update
https://www.nejm.org/doi/full/10.1056/NEJMra1905136
EffectsofIntermittentFastingonHealth,Aging,andDisease
Suppresses inflammation
Reduces obesity and type II diabetes
Protects against cardiovascular disease
Lowers risk of neurodegenerative disorders
Reduces cancer incidence
Animal models show consistent robust benefits of intermittent fasting:
Dec. 26, 2019
https://www.nejm.org/doi/full/10.1056/NEJMra1905136
Human studies show intermittent fasting ameliorates:
Dec. 26, 2019
 Obesity
 Dyslipidemia
 Hypertension
 Inflammation
 Insulin resistance
Effects of Intermittent Fasting on Disease Risk Markers
natureresearch October 27, 2020
Scientific Reports | (2020) 10:18341 | https://doi.org/10.1038/s41598-020-73767-w
“Intermittent fasting from dawn to sunset for 4 consecutive weeks
induces anticancer serum proteome response & improves
metabolic syndrome”
No eating/drinking between dawn and dusk…14-15 hours each day:
• 7.25 pounds of weight loss
• 8.8 mmHg reduction in blood pressure
• Significant increase in tumor suppressor/anticancer proteins
• Significant decrease in several tumor promoter/pro-cancer proteins
• Increasing a protein called calreticulin (by around 16 times)
• Calreticulin enhances IgG response to a SARS-CoV spike protein
“In the multi-variable model,
high adherence to the
Mediterranean diet was
associated with 25% lower
risk of death as compared
with the lowest category.”
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/mediterranean-diet-and-mortality-in-the-elderly-a-prospective-cohort-study-and-a-
metaanalysis/F2D6B083AA187849477112DB77820521
“Mediterranean diet and mortality
in the elderly: a prospective cohort
study and a meta-analysis”
Published online by Cambridge University Press: 30 August 2018
June 30, 2021
Mediterranean Diet Score, Dietary Patterns
and Risk of Sudden Cardiac Death
Study of 21,000 people over 9.8 years reveals:
 Diet high in fried foods, organ meats and processed meats regularly
had a 46% higher risk of sudden cardiac death compared to those
with least adherence.
 Those who most closely followed the traditional Mediterranean diet
had a 26% lower risk of sudden cardiac death than those with the
least adherence to this eating style.
Originally published
30 Jun 2021https://doi.org/10.1161/JAHA.120.019158
Journal of the American Heart Association. ;0:e019158
Mediterranean diet defined as high in vegetables and whole
grains, low intake of meat, high intake of marine omega-3s.
May 2008 Sept 2016
April 2015
Longevity Benefits of Mediterranean Diet
https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801
Mediterranean Diet Healthy Foods
More fruits, vegetables, and whole grains, and less dairy & meat than typical Western diet.
Foods to Reduce or Avoid
Re
 Red meat
 Overcooked meats
 Processed red meat (hot dogs, bacon)
 Butter
 Cured ham (nitrite/nitrite preserved meats)
 Most frozen meals
 Soda, desserts, candy
 Most processed foods
 Sugars
 Refined grains (white bread/white grain pasta)
 Excess salt
https://www.foodnetwork.com/healthy/articles/what-foods-are-not-allowed-on-mediterranean-diet
Baron Benjamin de Rothschild, heir
to a French banking fortune, died of
a heart attack at age 57 on January
15, 2021.
He oversaw the Edmond de Rothschild empire, which
has stakes in banks in France and Switzerland, owns
restaurants and hotels vineyards in Argentina, New
Zealand, South Africa, Spain and France.
Who missed the longevity boat?
Baron Benjamin de Rothschild
(1963 - 2021)
Expiration date: Jan. 15, 2021
net worth > $1.5 billion https://www.forbes.com/profile/benjamin-de-rothschild/?sh=401323666454
Age-standardized death rate
rate from heart disease per
100,000 people dropped:
Reduction in Heart Disease Mortality in the United States
68% decline over 45 years
From: 520 in 1969
To: 167 in 2014
Average American Died under age 70 in 1960
How to add 4.7 Years to Your Life Expectancy
The Omega-3-Index is a blood test that
can measure the percent of omega-3
fatty acids in red blood cells.
Red blood cell EPA/DHA content is a
good measure of sustained omega-3
status.
You want your Omega-3-Index score to
be > 6.8%
Typical Japanese Omega-3-Index is
> 8.0% that may correlate with 5 year
longer life expectancy in Japan.
Journal of Clinical Lipidology (2018) 12, 718-727 https://doi.org/10.1016/j.jacl.2018.02.010
People with omega-3 RBC scores > 6.8% compared with those < 4.2% :
39% lower risk for cardiovascular disease
34% lower risk of death from any cause
(Subjects average age 66 and followed over 7 years)
Higher Omega-3 Index associated with reduced risks because of:
1) Lowering of triglycerides, blood pressure, platelet aggregation, heart rate
2) Lower markers of inflammation and arterial plaque vulnerability
3) Reduced rate of telomere length attrition
December 2018
Omega-3-Index and Risk of Death
June 16th, 2021
The American Journal of Clinical Nutrition, nqab195, https://doi.org/10.1093/ajcn/nqab195
 Predictive model for correlation/association from Framingham Offspring Cohort (n= 2,240)
 Baseline omega-3-Index score and relevant covariates evaluated over 11-year follow-up.
 Standard risk adjustments: age, sex, total cholesterol, HDL cholesterol, hypertension
treatment, systolic blood pressure, smoking status, prevalent diabetes.
 Extensive validation process to account for confounding risk factors
Analysis reveals red blood cell omega-3 index over 6.8% in
people is associated with 4.7 years additional life expectancy
compared with omega-3 index under 4.2%.
Higher Omega-3 Blood Score =
Nearly 5 years increased Life Expectancy
July 27, 2021
Omega-3-Index scores in Life Extension® Supporters
 Only 1,300 mg of added EPA/DHA from fish/supplements moves Omega-3-Index from <4.2% to >6.8%
 Plant derived omega-3 precursors (ALA) not shown to achieve these robust EPA/DHA increases.
 Omega-3-Index at-home test costs $79 --- May save $$$ on fish oil supplements.
 Omega-3-Index test available at: www.LifeExtension.com/blood
Journal of Clinical Lipidology (2018) 12, 718-727 https://doi.org/10.1016/j.jacl.2018.02.010
Bridging the Longevity Gap
Urgent Need to Access Age-Reversal Interventions
Sheldon G. Adelson, a cabdriver’s son who built
the world’s largest empire of casinos and resort
hotels in Las Vegas, Macau, Singapore and other
gambling meccas.
The cause was complications of non-Hodgkin’s
lymphoma.
Donated to many charities including some that
supported medical research.
Who missed the longevity boat?
Sheldon Adelson
(1933 - 2021)
Expiration date: Jan. 11, 2021
net worth > $35.8 billion https://www.palmerfuneralhomes.com/obituary/Arthur-Decio
Stephen Bechtel Jr. led the Bechtel
construction empire for 30 years.
The Stanford-educated engineer became
a billionaire while leading BECHTEL’s
expansion through “mega-projects” in
Saudi Arabia, the U.S. and Canada.
Who missed the longevity boat?
Stephen Bechtel Jr.
(1925- 2021)
Expiration date: Mar. 15, 2021
Net worth > $3.5 billion https://www.bloomberg.com/news/articles/2021-03-16/stephen-bechtel-jr-heir-who-expanded-bechtel-group-dies-at-95
Who missed the longevity boat?
John C. Martin
(1951 - 2021)
Expiration date: Mar. 30, 2021
Net worth > $1.2 billion
https://www.fiercepharma.com/pharma/longtime-gilead-captain-john-martin-mastermind-life-saving-hiv-hcv-drugs-has-died
Credited for turning Gilead into $100 billion biotech giant.
Gilead developed a cure (Sovaldi®) for 95% of hepatitis C.
Died after apparent fall while walking home in Palo Alto.
“He was always driving us to do better.”
quoted Gilead executive
Risk of Delaying Human Research
Chronic Diseases May Negate Regenerative Benefits
July 14 ,2021
“Brain Implant Lets Man ‘Speak’ After Being Silent for More Than a Decade”
New England Journal of Medicine study shows brain implant in a stroke
paralyzed (15 years) patient enabled brain signals to be translated into words
on a computer screen.
https://www.nejm.org/doi/full/10.1056/NEJMoa2027540
Comment by expert on brain-computer interfacing:
Human Brain/Cloud Interface technologies will empower
us to preserve crucial brain information, interface our
brain directly with the cloud, positively impact learning,
and provide data for the study of consciousness. This
technology is not distant in the future, as many believe.
Nuno R.B. Martins, Ph.D. (July 28, 2021)
https://www.sciencedaily.com/releases/2019/03/190325120339.htm
March 29, 2019
Human Brain/Cloud Interface
Human brains
could be
connected to
the internet in
'next few
decades,'
scientists
predict
https://www.foxnews.com/science/human-brains-connected-internet-scientists-predict
April 15, 2019
"These devices would navigate the human
vasculature, cross the blood-brain barrier, and
precisely autoposition themselves among, or
even within brain cells," the study's senior
author, Robert Freitas, Jr., said.
"They would then wirelessly transmit encoded
information to and from a cloud-based
supercomputer network for real-time brain-
state monitoring and data extraction."
MANKIND COULD HAVE ELECTRIC IMMORTALITY
BY 2050
Human brains could be connected to the internet
in 'next few decades,' scientists predict
https://medicalxpress.com/news/2019-04-future-human-braincloud-interface-people.html
A future 'human brain/cloud interface' will give people
instant access to vast knowledge via thought alone
April 12, 2019
An international collaboration led by
researchers at UC Berkeley and the US
Institute for Molecular Manufacturing
predicts that exponential progress in
nanotechnology, nanomedicine, AI, and
computation will lead this century to
the development of a "Human
Brain/Cloud Interface", that connects
brain cells to vast cloud-computing
networks in real time.
Dr. Nuno Martins published paper Human Brain/Cloud Interface has attracted
enormous attention. Here is data from Frontiers of Neuroscience website:
More views than 90% of all “frontiers” articles
https://www.frontiersin.org/articles/10.3389/fnins.2019.00112/full
Significant relevance in neuroscience community. Frontiers in Neuroscience is world's
most-cited journal in the neurosciences field. (There are 67 “frontiers” journals.)
Human Brain/Cloud Interface paper has more views than 90% of ALL Frontiers articles.
Once this concept reaches critical mass…someone will likely make it happen.
March 29, 2019
Elon Musk’s Brain Computer Startup Raises
$205 Million from Google Ventures & Others
• Neurolink is trying to develop
high-bandwidth brain implants
that can communicate with
phones and computers
• Total investment in the company
now stands at $363 million.
July 30th, 2021
https://www.cnbc.com/2021/07/30/elon-musks-neuralink-backed-by-google-ventures-peter-thiel-sam-altman.html
• Survive until year 2045.
• Singularity enables neocortex to merge
with cloud-based artificial intelligence.
• Neocortex/AI enters limitless self-
improvement cycles.
Result is super-intelligence that advances
our abilities to incomprehensive levels
Ray Kurzweil’s Exit Plan to Immortality
December 17, 1903
First flight: 120 feet/20 feet off ground
December 17, 1903
International
Headline News
December 20, 1957
Intercontinental Air Travel
54 Years after Wright Brothers first in flight
April 9th 2021
https://www.wsj.com/articles/nasas-ingenuity-mars-helicopter-gets-set-for-historic-first-flight-on-another-world-11617465600?mod=searchresults_pos1&page=1
1903 2021
Exponential Advances in only 118 Years April 9, 2021
1903 - First “Flying Machine” travels 120 feet at Kitty Hawk
2021 - Robot + helicopter travel 140 million miles to Mars
2011- Cells from 100-year-old human fully rejuvenated1
2022 – Autologous iPSC studied for systemic rejuvenation
118 Years Later
11 Years Later
1. https://pubmed.ncbi.nlm.nih.gov/22056670/
1903 - First “Flying Machine” travels 120 feet
2021 - Robot + helicopter travel 140 million miles to Mars
1997- Longest lived human (J.Calment) dies at age 122
(118 Years Later)
What if Human Lifespans increase at same rate as Aviation/Space Travel?
2045(?) – Escape velocity yields 739-billion-year lifespans
https://www.youtube.com/watch?v=BPKHHQFI-WM
• Old Fibroblasts + Yamanaka-like factors = Autologous Pluripotent Cells
• Remove senescent cells from bone marrow niche.
• Repopulate bone marrow niche with autologous hematopoietic and
mesenchymal stem cells.
• Hematopoietic stem cells reverse immune senescence and anemia without
“graft vs host” concerns because genetic profile virtually identical to host.
• Mesenchymal stem cells systemically regenerate tissues.
• Study objective: Systemic age-reversal + immune restoration in humans.
Recap of Human Age Reversal Research Initiative
(Large animal pilot studies will first evaluate safety and regenerative efficacy)
B. Wayne Hughes, co-founder of
largest self-storage company.
Founded in 1972 with $50,000.
Public Storage value: $56 billion.
Donated money to cancer research.
Dead at age 87.
Who missed the longevity boat?
B. Wayne Hughes
(1933 - 2021)
Expiration date: Aug, 18, 2021
net worth > $4.1 billion https://www.forbes.com/sites/michelatindera/2021/08/18/b-wayne-hughes-billionaire-founder-of-public-storage-dies-at-
87/?sh=17193a5f42fe
Apple News - July 11, 2021
“Can Science Cure Death?
It Sure Looks Like It”
“The World Health Organization added
a distinction that characterizes aging
as a disease.”
https://apple.news/A4LOishZsQQ2xGEgHrlSCxA
“Saraev, like any number of young optimistic
tech-associated men believes that if he takes
the correct preventative steps now, he might
well live forever.”
Carnegie Mellon’s Cloud Lab to Automate Labor-Intensive Science Exp
August 31, 2021
• $40 million laboratory designed to automate lab
experiments with robotics and artificial
intelligence.
• Experiments carried out remotely by about 200
different types of AI robotic machines.
• Scientists from around the world can synthesize,
or create, molecules using a robot based in
Switzerland.
“The benefit comes in accelerating science”
https://www.wsj.com/articles/carnegie-mellons-cloud-lab-to-automate-labor-intensive-science-experiments-11630348526?mod=searchresults_pos2&page=1
Sept 4, 2021
“…Silicon Valley’s
latest wild bet on
living forever”
https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/
World’s Largest Anti-Aging Organization
https://www.lifeextension.com/about/life-extension-story/history
 First to introduce DHEA to delay systemic aging (1981)
 First to introduce aspirin to prevent heart attack (1983)
 First to introduce coenzyme Q10 to reverse heart failure (1983)
 First to introduce cimetidine as adjuvant cancer therapy (1986)
 First to introduce melatonin to improve immune function (1992
Life Extension Magazine
September 2021
Unparalleled Track Record
of Biomedical Innovation
Established 1977
Copyright ©Life Extension®. Confidential and proprietary.
How I Fund Age Reversal Research
Supplement Sales Support Rejuvenation Projects
age-reversal.net
This entire presentation available at:
181
“They’re not fond of rules. And they have no
respect for the status quo.”
“You can’t ignore them. Because they change
things. They push the human race forward.”
“People who are crazy enough to think
they can change the world, are the ones
who do.”
Steve Jobs
Excerpts from “Think Different”
campaign 1997
Prospect of
Human Age Reversal
William Faloon
RAADFest
October 2nd, 2021

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Bill Faloon's Keynote Speech from RAADfest 2021

  • 1. Prospect of Human Age Reversal William Faloon RAADFest October 2nd, 2021
  • 3.  Biomedical research findings since last year's RAADfest.  What people can do now to live 5 more years.  Repopulate bone marrow with autologous induced hematopoietic stem cells to reverse immune senescence.  Transhumanist advances over last few months. Transcending Towards Immortality Today’s overview…
  • 4. Life Extension® was born in January 1977  Life Extension® incorporated in 1977 in Florida.  First published in 1980. (Anti-Aging News)  World’s largest anti-aging organization…over 400,000 supporters. (2021) Life Extension Center-Pompano Beach, Florida (1977)
  • 6.
  • 7.
  • 8.
  • 9. 1980-1986-Anti-Aging News 1986-1994-Life Extension Report 1994-2021-Life Extension Magazine 41 Consecutive Years of Monthly Publication (419,000 copies mailed last month)
  • 10. Our Controversial Contention It may be possible… To Reverse Aging in Humans Today www.age-reversal.net
  • 11. “In the Search to Stall Aging, Biotech Startups Are Out for Blood” May 13, 2021 https://www.smithsonianmag.com/innovation/in-search-to-stall-aging-biotech-startups-are-out-for-blood-180977728/ Mixing young and old blood flows
  • 12. Black Circles = Rats Given Young Plasma --- White Circles = Control Rats Young Plasma Treated Rats Live Healthier and Longer Than Control Group Young Plasma Group Control Group
  • 13. AGE: 31.8 months Control (left) Young plasma (right) CONTROL
  • 14. AGE: 31.8 months 1 control 3 young plasma
  • 16. AGE: 34.5 Months: Two Young Plasma Treated Rats and Control in Middle TREATED TREATED CONTROL
  • 17. Survival + Quality of Life Improvements in rats receiving Young Plasma (i.p.) every 2 weeks Control Group At 29 months untreated rats start rapid Die Off u Treatment Group Rats aged human equivalent of 60 years given Young Plasma via Intraperitoneal injection. Transient improvement in quality of life. Average Lifespan of untreated group: 29.8 months (70 years in humans) Average Lifespan of Treated group: 32 months (77 years in humans) On May 23, 2021, seven treated rats alive compared to one living control. On July 20, 2021, two treated rats alive compared to one living control. Email from Professor Rodolfo Goya to Bill Faloon- August 16th, 2021 Plasma Treated Rats Start Die Off at 31 months Age (months) 34 27 28 33 32 31 29 30 26 25 34
  • 18. Conclusions: Young plasma seems to possess revitalizing factors able to remarkably improve the quality of life of old rats and moderately extends their lifespan.
  • 19. DNA methylation controls the transcription (activation) of genes. Without proper DNAmethylation, beneficial genes are deactivated while harmful genes can be over-expressed. DNA Methylation measures Epigenetic Age Young plasma treatment more than halved epigenetic ages. This is the principal of what is called “epigenetic aging.” Horvath,S.,Singh,K.,Raj,K.,Khairnar,S.,Sanghavi,A.,Shrivastava,A.,...&Lehmann,M.(2020),. Reversing age: dual species measurement of epigenetic age with a single clock. bioRxiv
  • 20. How to Transition Young Plasma Benefits into Old Humans?
  • 21. Bone Marrow Yields Regenerative Stem Cells Bone Marrow Stem Cell Niche Bone Marrow Cell Production Essential to Sustain Life Hematopoietic Stem Cells Mesenchymal Stem Cells +
  • 22. Stem Cells Naturally Enable Systemic Rejuvenation But our supply of hematopoietic and mesenchymal stem cells is limited. Transcription Factors can reprogram old cells into induced pluripotent stem cells that can theoretically regenerate our tissues forever.
  • 23. Transcription factors turn our genes “on” and “off ”...so, they are expressed in the right cell, at the right time, and in the right amount.
  • 24. The Nobel Prize in Physiology or Medicine 2012 John B. Gurdon and Shinya Yamana “For the discovery that mature cells can be reprogrammed to become pluripotent.” The Nobel Prize recognizes two scientists who discovered that mature, specialized cells can be reprogrammed to become embryonic cells capable of developing into all tissues of the Four specific genes encode transcription factors that can convert somatic cells into pluripotent stem cells that can propagate indefinitely. These transcription factors are collectively called: “Yamanaka Factors” https://www.nobelprize.org/prizes/medicine/2012/yamanaka/facts/
  • 25. Hematopoietic Stem Cell https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hematopoietic-stem-cell Hematopoietic stem cells develop into all types of blood cells and are found in peripheral blood and bone marrow. With age, hematopoietic stem cells become depleted and contribute to immune senescence and anemia. Healthy hematopoietic stem cells needed to sustain life.
  • 26. February 2017 https://www.nature.com/articles/ncomms14533 “How blood can be rejuvenated”  Blood stem cells generate around a thousand billion new blood cells every day.  The capacity of hematopoietic stem cells to produce new blood cells diminishes with age.  Older people more susceptible to anemia, lowered immunity, and blood cancers.  Researchers at Lund University (Sweden) rejuvenate blood stem cells in aged mice. “We found that there was no difference in blood-generating capacity when we compared the reprogrammed blood stem cells with healthy blood stem cells from a young mouse. This is, as far as we know, the first time someone has directly succeeded in proving that it is possible to recreate the function of young stem cells from a functionally old cell.”
  • 27. Transplanting Hematopoietic Stem Cells into Old Mice Yields Restoration of Blood Cell Production https://www.nature.com/articles/ncomms14533/figures/1
  • 28. February 28, 2021  This 2021 published review and additional investigations summarize age-reversal impact of cell reprograming.  Human trials being investigated  Funded by Bill Faloon and other charitable donors https://pubmed.ncbi.nlm.nih.gov/33627519 “When cells were reprogrammed with a 6-factor cocktail the (degenerative) alterations were fully reversed and cells fully rejuvenated.”
  • 29. Elderly Human Experimental Approach to Reverse Systemic Aging Reprogram Old Functional Cells into Autologous Pluripotent Stem Cells
  • 30. Old Somatic Cells Remove somatic (fibroblast) cells
  • 31. Potential Systemic Regeneration using Induced Pluripotent Stem Cell Therapy Somatic Cells Induced Pluripotent Stem Cell-based Therapy Cellular Reprogramming adding NANOG + LIN28 Yamanaka Factors Purification of induced progenitors to remove non-differentiated iPSCs Autologous iPSC (Induced Pluripotent Stem Cells) Old fibroblasts reprogrammed into autologous induced pluripotent stem/progenitor cells iPSC-derived progenitor cells
  • 32. Step 1: Selectively remove senescent bone marrow cells. Step 2: Replace with induced autologous pluripotent hematopoietic stem cells to rebuild immunity. Step 3: Also use transcription factors to make autologous mesenchymal stem cells for systemic regeneration. Rebuild Bone Marrow to Restore Youth Human Research Initiative: Large animal pilot studies will first evaluate safety and regenerative efficacy.
  • 33. “Young bone marrow rejuvenates aging mouse brains, study finds” Microglia in brains of old mice have fewer/shorter branches than young mice Available at: https://medicalxpress.com/news/2019-02-young-bone-marrow-rejuvenates-aging.html. Feb. 20, 2019 Synaptic branches of microglia of old mice who received bone marrow transplants from young mice resembled those of young mice
  • 34. Young bone marrow transplants restore exploratory activity in old mice Feb. 20, 2019 “Remarkably, young bone marrow recipients, but not old bone marrow recipients, were more active than old control mice.” https://www.nature.com/articles/s42003-019-0298-5/figures/1
  • 35. March 2020 Overall Mortality Reduced by 58% Median Lifespan Increased 12% in Aged Mice “The increase in longevity was accompanied by reductions of frailty…Our findings have implications for further development of stem cell therapies for increasing health and lifespan.” Intervention: Old hematopoietic stem cells replaced with young‐donor hematopoietic stem cells using novel mobilization‐enabled hematopoietic stem cell transplantation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059148/
  • 36. May 14, 2021 Four Transcription Factors Increase Longevity in Whole Animals Progerin producing mice treated early in life with “transcription factors “had improved tissue structures in bone, lung, spleen, kidney and skin, with an increased lifespan of 15%, associated to a differential DNA methylation signature. Maximum lifespan increased in certain groups (61 weeks…11 weeks longer than longest lived animals) “Altogether, our results indicate that a single short reprogramming early in life might initiate and propagate an epigenetically related rejuvenated cell physiology, to promote a healthy lifespan.” https://www.biorxiv.org/content/10.1101/2021.05.13.443979v1
  • 37. https://www.creative-biolabs.com/stem-cell-therapy/mesenchymal-stem-cells-mscs-differentiation- services.htm?gclid=CjwKCAjw9aiIBhA1EiwAJ_GTStzlhTD64Q3aZTnBjCMQmkDRggtvmM9G1k0DWD3yZIutOQe6TuLOnxoCLvkQAvD_BwE Mesenchymal Stem Cells (MSCs) Differentiation Services A company that offers MSC differentiation services. Mesenchymal stem cells (MSCs) are undifferentiated multipotent cells that possess potential in tissue regeneration and cell-based therapy due to their multipotency. Application of MSCs requires their isolation and direction of their differentiation into the appropriate lineage. Creative Biolabs offers customized services for reliable in vitro induction of MSCs into osteogenic, adipogenic, muscular, and chondrogenic lineages.
  • 39. Fibroblast cells make up extracellular matrix and collagen. Cell reprogramming converted old fibroblasts into induced autologous pluripotent stem cells. In vivo research seeks to repopulate bone marrow niche with induced autologous hematopoietic and mesenchymal stem cells (from old autologous fibroblasts). Objective: Reverse immune senescence and rejuvenate tissues. Research Project: In vivo Human Study Using Induced Hematopoietic and Mesenchymal Stem Cells Derived from Autologous Fibroblasts Skin Derived Fibroblast Cell r
  • 40. Yamanaka Factors Potential Systemic Regeneration Using Induced Pluripotent Stem Cell Therapy Cellular (Induced Pluripotent Stem Cells) Induced Pluripotent Stem Cell-based Therapy iPSC-derived progenitor cells Old fibroblasts reprogrammed into autologous induced pluripotent stem/progenitor cells Cellular Reprogramming adding NANOG + LIN28 Elderly Purification of induced progenitors to remove non-differentiated iPSCs
  • 41. Apple News - July 11, 2021 “Can Science Cure Death? It Sure Looks Like It” “The World Health Organization added a distinction that characterizes aging as a disease.” https://apple.news/A4LOishZsQQ2xGEgHrlSCxA “Saraev, like any number of young optimistic tech-associated men believes that if he takes the correct preventative steps now, he might well live forever.”
  • 43. October 17th 2020 “This Japanese Engineer Created the Robots That Make Your Created $40 Billion Company Dies in 2020 at age 95 Mr. Inaba read a 1952 article in Scientific American describing rudimentary computer program that told a machine how to carve up a piece of metal. He advanced this early MIT technology into “programmable machine tools” that enable today’s computer-driven assembly lines. https://www.wsj.com/articles/this-japanese-engineer-created-the-robots-that-make-your-cars-11602856803 Genesis of this Breakthrough was year 1952 Scientific American article!
  • 44. https://www.scientificamerican.com/article/aging-is-reversible-at-least-in-human-cells-and-live-mice/ “New research suggests it is possible to slow or even reverse aging, at least in mice, by undoing changes in gene activity—the same kinds of changes that are caused by decades of life in humans.”
  • 45. What’s Transpired Since RAADfest 2020? October 2nd - 4th 2020
  • 46. Sept 30, 2020 British billionaire Jim Mellon plans to take his life extension start-up public in six to 12 months “Juvenescence has raised about $170 million privately and still has a “fair amount of money left in the bank.” “Mellon isn’t the only billionaire who wants to live beyond a hundred. Michael Bloomberg, told Business Insider in 2017 he wants to live until he’s 125.” https://www.cnbc.com/2020/09/29/billionaire-jim-mellon-plans-to-take-life-extension-start-up-public.html#:~:text=LONDON%20%E2%80%93%20British%20billionaire%20Jim%20Mellon,to%20extend%20the%20human%20life. Jim Mellon Born: February 1957
  • 47. “Plasma dilution improves cognition and attenuates neuroinflammation in old mice” “Explaining the mechanism of the positive effects of neutral blood exchange on the brain, our comparative proteomics analysis demonstrated that dilution of old blood plasma yields an increase in the determinants of brain maintenance and repair in mice and in people. These findings confirm the paradigm of rejuvenation through dilution of age-elevated systemic factors and extrapolate it to brain health and function.” https://link.springer.com/article/10.1007/s11357-020-00297-8 November 15, 2020
  • 48. https://medicalxpress.com/news/2020-11-hyperbaric-oxygen-treatments-reverse-aging.html “Study finds hyperbaric oxygen treatments reverse aging process” A new study from Tel Aviv University and the Shamir Medical Center in Israel indicates that hyperbaric oxygen treatments in healthy aging adults can stop the aging of blood cells and reverse the aging process. In the biological sense, the adults' blood cells actually grow younger as the treatments progress. November 20, 2020 v Tel Aviv University
  • 49. Research Paper Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial Yafit Hachmo1, * , Amir Hadanny2,3,4, * , Ramzia Abu Hamed1 , Malka Daniel- Kotovsky2 , Merav Catalogna2 , Gregory Fishlev2 , Erez Lang2 , Nir Polak2 , Keren Doenyas2 , Mony Fri edman2 , Yonatan Zemel2 , Yair Bechor2 , Shai Efrati1,2,3,5 •1 Research and Development Unit, Shamir Medical Center, Zerifin, Israel •2 The Sagol Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center, Zerifin, Israel •3 Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel •4 Bar Ilan University, Ramat-Gan, Israel •5 Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel * Equal contribution https://www.aging-us.com/article/202188/text AgING November 18, 2020
  • 50. November 19, 2020 “It Sure Looks Like Humans Have Found a Way to Reverse Aging” https://www.popularmechanics.com/science/health/a34730692/study-reverse-aging-in-humans/ “A landmark study shows the reversal of biological aging in humans.” “The researchers used oxygen therapy in a pressurized chamber to reverse aging in two key biological clocks.” “The study showed lengthening in the telomeres of chromosomes and a decrease in (senescent) cells known to cause aging.”
  • 51. Novel Hyperbaric Oxygen Protocol Extends Telomere Length and Improves Immune Markers Some immune cell telomeres elongated by 20%. Some senescent immune cells reduced by 37%. Improved immune markers. https://www.aging-us.com/article/202188/text
  • 52. “Human ageing process biologically reversed in world first” 1, https://www.telegraph.co.uk/news/2020/11/18/human-ageing-process-biologically-reversed-world- first/#:~:text=The%20ageing%20process%20has%20been,that%20comes%20with%20growing%20older November 18, 2020 “The aging process has been biologically reversed for the first time by giving humans oxygen therapy in a pressurized chamber.”
  • 53. 1, https://www.telegraph.co.uk/news/2020/11/18/human-ageing-process-biologically-reversed-world- first/#:~:text=The%20ageing%20process%20has%20been,that%20comes%20with%20growing%20older November 18, 2020 “Scientists said the growth may mean that the telomeres of trial participants were now as long as they had been 25 years earlier.”
  • 54. Aviv Clinic The Villages, FL 32163 https://aviv-clinics.com/hyperbaric-centers/villages-florida/ First Hyperbaric Chamber Clinic of its Type Opens in Central Florida
  • 55.
  • 56. Total cost is $45,000 broken down into two installments: - $15,000 to initiate 3 days of evaluations including advanced brain imaging, cardiopulmonary testing, diagnostic and functional assessments. - $30,000 to begin a 3-month, multi-modality treatment regimen with hyperbaric oxygen, including post treatment and monitoring. Aviv Clinics Center for Advanced Healthcare 2955 Brownwood Blvd., Suite 100 The Villages, FL 32163 Downside: Need to be physically near Central Florida
  • 57. Hyperbaric Treatment Protocol  Five daily sessions a week for 3 months  Each session involved breathing 100% oxygen by mask for 90 minutes with 5- minute air breaks every 20 minutes.  Each total session time about 2 hours.  Commercial price for 60 sessions: $18,000 https://www.aging-us.com/article/202188/text
  • 58.
  • 59.
  • 60. House of Optimal Health - Hormones - Kidney function - LDL/HDL - Vitamin D - Blood Pressure - Glucose - C-reactive protein - Homocysteine - Insulin - Coagulation Level 2 Level 1 - Senolytics - NAD+ Restoration - mTOR-inhibition - Exosomes - Stem Cells - Hyperbaric Oxygen - Young Plasma Failure to optimize Level 1, preclude benefits of Level 2. Age Reversal Interventions Healthy Aging - Perinatal Tissues
  • 61. December 1, 2020 “Drug reverses age-related cognitive decline within days” DOI: 10.7554/eLife.62048 UC San Francisco scientists show a few doses of new small-molecule integrated stress inhibitor:  Rapid restoration of cognitive function in aged mice  Reverse cognitive impairments in Down Syndrome  Restore memory function after traumatic brain injury  Prevent noise-related hearing loss  Immune cell rejuvenation  Enhanced cognition in healthy mice https://medicalxpress.com/news/2020-12-drug-reverses-age-related-cognitive-decline.html “Just a few doses of an experimental drug can reverse age- related declines in memory and mental flexibility in mice”
  • 62. December 3, 2020 https://www.nature.com/nature/volumes/588/issues/7836 “Reprogramming retinal cells can reverse age-related vision loss”  Harvard researchers use three Yamanaka transcription factors to reprogram retina cells to a more youthful epigenetic state.  The transcription factors restored youthful DNA methylation patterns.  Old mice with damaged optic nerves grew new axons and reversed vision loss in this model of glaucoma. “These results show that mammalian tissues retain a record of youthful information, encoded in part by DNA methylation, which can be accessed to improve tissue function and potentially to reverse the effects of aging.”
  • 63. Nature 588, 34-36 (2020doi: https://doi.org/10.1038/d41586-020-03119-1) Restoring Vision in Mice via Axon Regeneration natur e December 2, 2020 Restoring vision in mice. Retinal ganglion cells (RGCs) transmit visual information from the eye to the brain along projections called axons. Damage to the RGC axons prevents transmission of this information, leading to sight loss. Lu et al.2 report that treatment of damaged RGCs with a transcription-factor cocktail called OSK restores the cells to a youthful state, leading to axon regeneration and restoration of sight in mice.
  • 64. December 30, 2020 https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/ “Cracking the code of biological aging could solve America’s health care crisis” “The most exciting opportunity for such an improvement in health productivity is to understand and address the biology of aging.”
  • 65. Dec. 30, 2020  Therapeutic Plasma Exchange---Conboy Lab-UCBerkeley  Thymic Regeneration---Greg Fahy-InterveneImmune  Reverse extra-cellular protein stiffening (glycation) Age-Reversal Interventions Highlighted: https://www.sciencedirect.com/science/article/pii/S1568163720302324 https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/
  • 66. “With such treatments, Americans would experiencemorehealthy,productiveyearsoflife.” “Withouttreatmentstosloworreverse aspects of biologicalaging,anagingpopulationmeans we areinfor ahealthcarecosttsunami.” Dec. 30, 2020 https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/ Mainstream Recognition of The Need to Reverse Human Aging
  • 67. “…why not launch an Operation Warp Speed for biological aging?” CONCLUSION https://fortune.com/2020/12/30/anti-aging-research-health-care-spending-biden/ December 30, 2020
  • 68.
  • 69. Scientists have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research. “The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.” Jianfeng Lan, Jarod A. Rollins, Xiao Zang, Di Wu, Lina Zou, Zi Wang, Chang Ye, Zixing Wu, Pankaj Kapahi, Aric N. Rogers, Di Chen. Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity. Cell Reports, 2019; 28 (4): 1050 DOI: 10.1016/j.celrep.2019.06.078 “Pathways that extend lifespan By 500 percent identified” Jan 8, 2020
  • 70. “In fact, the two pathways which the team manipulated—known as the insulin signaling and TOR pathways—are also found in people. SCIENTISTS EXTENDED THE LIFESPAN OF THESE ANIMALS BY 500 PERCENT Jan 9, 2020 https://www.newsweek.com/scientists-extend-lifespan-animals-500-percent-1481241 This means that the latest results could have implications for the development of new anti-aging therapies.”
  • 71. Age Reversal Interventions Autophagy Inflammation Remove senescent cells Restore youthful methylation Lengthen telomeres AMPK/ mTOR Sirtuins/ NAD+ Exosomes Hyperbaric
  • 72. https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054 “…mice with progeria that got the gene-editing treatment lived more than twice as long as the untreated mice.” CRISPR Gene-Editing Treatment Jan7,2021
  • 73. CRISPR-Treated Progeroid Mouse 17 Months >160 Years? 7.1 Months Combination CRISPR-Treated Human Untreated Progeroid Mouse https://www.nature.com/articles/s41586-020-03086-7 https://doi.org/10.1073/pnas.1910073116 Extrapolation Assuming Multi-Gene Edits in Normal Aged People via CRISPR
  • 74. 1) 25% extended lifespan in normal aged mice.1 2) Improved overall appearance and grip strength.1 “A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence” January 6, 2021 1. https://stm.sciencemag.org/content/13/575/eabd2655/tab-pdf 2. https://www.genome.gov/10001345/importance-of-mouse-genome Mice and humans share virtually the same set of genes though in slightly different forms.2 KAT7 gene is significant driver of cell senescence. Targeting KAT7 using CRISPR enabled:
  • 75. 98-Year Average Lifespan? 25% Lifespan Extension It May Be Possible for Normal Aged People to Benefit from these Kinds of Single-Gene CRISPR Edit If this CRISPR-Treatment Works Similar in Normal Aged Humans CRISPR-Treated NormalAged Mouse Science Translational Medicine. 06 Jan 2021:Vol. 13, Issue 575, eabd2655. DOI: 10.1126/scitranslmed.abd2655
  • 76. https://www.dailymail.co.uk/sciencetech/article-9166007/Chinese-scientists-develop-gene-therapy-delay-ageing.html Mainstream News Coverage of CRISPR Longevity Study January 21, 2021 “A new gene therapy has been shown to reverse some of the effects of aging in mice and extend their lifespans by up to a quarter.”
  • 77. Covid shows that aging is like a disease —we should treat it accordingly January 22, 2021  “Covid-19 may be a disease of aging, as well as a respiratory illness.  … some anti-aging therapies could prove as important in the 21st century as antibiotics were in the 20th.  The pandemic has left people more frightened than ever about getting old…it has also left clues that could prompt a revolution in how we think about aging.”
  • 78. https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging “Fueled in part by a billion dollars of investor money, they are attempting to reverse-engineer your molecular biological clock. Their goal? To eliminate not merely diseases that kill people, but to prevent death itself.” Feb 20, 2021 Is There a Cure for Aging?
  • 79. https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging Feb. 20, 2021 “the immortal jellyfish...cheats death by reverting from adulthood back to its polyp stage when threatened with danger or starvation.” “and lobsters' stock a seemingly limitless supply of a youthful enzyme that has some scientists wondering if the crustacean, under the best conditions, just might live forever.” “…the immortal jellyfish” (Turritopsis dohrnii)
  • 81. February 20, 2021 “I don’t see why eliminating a disability or giving a kid blue eyes or adding 15 IQ points is truly a threat to public health or to morality,” says the Harvard gene-editing pioneer George “The new biotechnology called CRISPR offers the prospect of defeating lethal viruses and curing genetic diseases, even as it raises serious moral questions.”
  • 82. C = Clustered R = Regularly I = Interspaced S = Short P = Palindromic R = Repeats CRISPR is a family of DNA sequences found in genomes of prokaryotic organisms such as bacteria
  • 83. CRISPR Gene-Editing Treatment An untreated progeria mouse at 7.5 months of age, with a thin, grayish coat, pronounced spinal curvature, and low activity levels. Untreated progeria mice have an average lifespan of 7.1 months. Three treated progeria mice at 11 months of age, with healthy coats, no apparent spinal curvature, and normal activity levels. The treated progeria mice had an average lifespan of 17 months. CRISPR-Edited Progeroid Mice Unedited Rapid-Aged Mouse https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
  • 84. CRISPR Therapy Corrects Pathologic Mutations in DNA Genes Healthy Longevity Conferred by Replacing Progeroid DNA base pair T and A with Normal C and G DNA base pair https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
  • 85. 1. A ‘base editor’ was designed to home in on this mutation and correct it to the normal sequence. The molecule was put into a special inactivated virus. How this Gene Editing Therapy Extended Life https://www.wsj.com/articles/crispr-gene-editing-treatment-could-point-way-to-fix-for-deadly-aging-disease-11609950054
  • 87. Untreated Progeroid Mouse CRISPR-Treated Progeroid Mouse 7.1 months 17 months Combination CRISPR-Treated Human > 160 Years? https://www.nature.com/articles/s41586-020-03086-7 https://doi.org/10.1073/pnas.1910073116 Extrapolation Assuming Multi-Gene Edits in Normal Aged People via CRISPR
  • 88. Results from single dose combination gene therapy: Noah Davidsohn, Matthew Pezone, Andyna Vernet, Amanda Graveline, Daniel Oliver, Shimyn Slomovic, Sukanya Punthambaker, Xiaoming Sun, Ronglih Liao, Joseph V. Bonventre, and View ORCID Profile George M. Church PNAS November 19, 2019 116 (47) 23505-23511; https://doi.org/10.1073/pnas.1910073116 November 19, 2019 1)58%increasedfunctionafterheartfailure 2)38%reductioninvasculardiseasemarker 3) 75% reduction in kidney atrophy 4)Complete reversal ofobesity &diabetes
  • 89. George Church https://www.52-insights.com/interview-george-church-playing-god-with-our-genes-science/ May 4, 2018 “We’ve been doing aging reversal on a variety of different traits — cardiac disease, kidney, obesity, diabetes…and we have examples of gene therapies that can affect all of these simultaneously.” “I think we’re talking about in the next few years seeing an aging reversal in 12-year- old dogs.”
  • 91. DEC. 8, 2019 “A Harvard geneticist's goal: to protect humans from viruses, genetic diseases, and aging” “George Church's lab at Harvard Medical School is working to make humans immune to all viruses, eliminate genetic diseases and reverse the aging process…”
  • 92. March 2, 2021 https://www.sciencealert.com/experimental-crispr-treatment-cuts-cholesterol-in-mice-by-up-to-57-in-single-shot “In addition to the cholesterol reduction, the experiment produced a 29.4% decrease in triglycerides…” CRISPR May Eliminate Need for Drugs Single CRISPR Injection reduces cholesterol Up to 57% in Mice
  • 93. https://www.nytimes.com/2021/03/08/books/review/walter-isaacson-the-code-breaker.html 2020 Nobel Prize in Chemistry awarded to Jennifer Doudna and Emmanuelle Charpentier for CRISPR-cas9 research “Gene Editing, and the Future of the Human Rac “The landmark research …has the potential to control future pandemics — either by outwitting the next viral plague through better screening and treatment or by engineering human beings with better disease resistance programmed into their cells.” March 8 2021
  • 94. https://www.webmd.com/healthy-aging/story/is-there-a-cure-for-aging February 20, 2021 “If the results are what they think they will be, the whole world could go on metformin and extend life for everybody.” - Nir Barzilai, lead researcher on “Targeting Aging with Clinical Trial”
  • 97. “Can some drugs delay aging? Scientists focus on tho that target frailty and age-related disease.” March 6, 2021 “Leading the list of candidates is metformin, a longtime treatment for type 2 diabetes, and rapamycin, a chemotherapy agent and immunosuppressant. Scientists also are studying a class of compounds known as senolytics, which attack ‘senescent’ cells in the body that tend to proliferate with age.” https://www.washingtonpost.com/health/anti-aging-drugs-metformin-study/2021/03/05/d9de870a-7882-11eb-9537-496158cc5fd9_story.html FDA has approved a second clinical trial using metformin to target frailty in people over age 65 in San Antonio area.
  • 98. Lifestyle Intervention Plus Metformin to Treat Frailty in Older Veterans With Obesity • Third clinical trial receives FDA approval • Location: Houston, TX • Status: Recruiting - Older adults (65 to 85 years) - Groups: • Diet-induced weight loss and Exercise Training plus Metformin • Diet-induced weight loss and Exercise Training plus Placebo • Healthy lifestyle and Metformin - Outcome Measures: • Improvements in physical function, bone mineral density and bone quality, lean body mass and muscle quality, and markers of senescence-associated phenotype (SASP). Additional information: https://clinicaltrials.gov/ct2/show/NCT04221750
  • 99. “Reversal of epigenetic aging and immunosenescent trends in humans.” Aging Cell; Sept 2019 Thymic Age Reversal Demonstrated in 2019 1) Human growth hormone 2) DHEA 3) Metformin Study conducted by Dr. Greg Fahy in collaboration with researchers from Stanford University and UCLA used individualized doses of: Study subjects also provided with daily vitamin D3 and zinc.
  • 100. https:// www.dailymail.co.uk/health/article-7435427/ Oct.22,2019 Turning Back Time! “Aging is REVERSED in men using a cocktail of growth hormones and diabetes drugs in study that saw test group shed 2.5 biological years.”
  • 101. Life Extension Magazine recommended metformin 26 years ago…the FDA went berserk! March 1995
  • 103. Example of Lethal Delay https://www.longevity.technology/worlds-first-anti-aging-trial-gets-green-light/ Sept 4, 2019 1958 - Metformin approved as anti-diabetic drug in England 1995 - Life Extension® lists metformin as anti-aging drug 2015 - FDA approves first anti-aging study of a drug (metformin) 2019 - Metformin study receives $75 million funding ($40 million from anonymous donor)
  • 104. Bridging the Longevity Gap Urgent Need to Access Age-Reversal Interventions
  • 105. New CRISPR Technique Might Edit Epigenetics • Highly specific DNA methylation • Does not alter DNA sequence • Changes DNA methylation (epigenetic) marks • Epigenetic changes persist into cell differentiation to stem cells. • Might enable altering of cellular “epigenetic age” Reference: Nuñez et al. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell. 2021 Apr 7;S0092-8674(21)00353-6. doi: 10.1016/j.cell.2021.03.025. April 7, 2021 “An on-off switch for methylation editing”
  • 106. Reference: Nuñez et al. Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing. Cell. 2021 Apr 7;S0092-8674(21)00353-6. doi: 10.1016/j.cell.2021.03.025. Control gene expression with high specificity while leaving DNA sequence unchanged. April 7, 2021  “CRISPR on” can activate target genes with high specificity  “CRISPR off” can deactivate genes with high specificity New Technology called “CRISPR 2.0”:
  • 107. https://www.longevity.technology/michael-greve-commits-e300m-for-rejuvenation-start-ups/ Michael Greve commits €300m for rejuvenation start- ups The founder of Forever Healthy has committed to advance rejuvenation biotech start-ups With this €300 million ($360 million) commitment, Greve intends to accelerate the advent of rejuvenation biotechnology with new, repair-based approaches that treat the root causes of aging… Human rejuvenation is not science fiction anymore and resulting therapies are affordable and uncomplicated. May 6, 2021
  • 108. mTOR Inhibition with rapamycin Improves Alzheimer’s in Mouse Model of Disease Effects of rapamycin in mouse model of Alzheimer’s: Van Skike et al. mTOR attenuation with rapamycin reverses neurovascular uncoupling and memory deficits in mice modeling Alzheimer's disease. J Neurosci . 2021 Apr 20;JN-RM-2144-20. doi: 10.1523/JNEUROSCI.2144-20.2021. PMID 33888602. April 20, 2021 •Improved cerebrovascular function (better than non-Alzheimer’s mice) •Reduction of beta-amyloid in brain cortex •Reversed memory deficits
  • 109. Rapamycin Human Study Receives $485,000 Funding  Randomized, placebo-controlled trial into the safety/efficacy of rapamycin in reducing clinical measures of aging in an older adult population.  Two differing doses: 5 mg or 10 mg of rapamycin one time a week or placebo.  Primary Outcome Measure: Changes in visceral fat as measured by (DXA) scan.  Secondary Outcomes: Range of clinical measures, e.g. bone density, blood tests, etc.  20 people enrolled at $360 each (original cost before donations was $1,200). Sponsor: AgelessRx Collaborator: University of California, Los Angeles Principal investigators: James Watson, M.D. and Sajad Zalzala, M.D. June 18, 2021 To enroll log on to: https://www.agelessrx.com/pearl
  • 110. Senolytic Enhances Kidney Regeneration in Mice Senolytic treatment with ABT-263: • Reduced senescent cell numbers • Restored regenerative profile in aged mouse kidney • Improved kidney function2 1. https://www.kidney.org/news/monthly/wkd_aging 2. Mylonas K et al. Cellular senescence inhibits renal regeneration after injury in mice, with senolytic treatment promoting repair. Sci Transl Med. 2021 May 19;13(594):eabb0203. doi: 10.1126/scitranslmed.abb0203. PMID 34011625. May 19, 2021 More Than 50% of Americans over age 75 Are Believed to Have Kidney Disease1
  • 111. June 1, 2021 Buck Institute Announces Non-Invasive Test to Measure Senolytic Efficacy Precise measure of senescent cell destruction demonstrated in cell culture and mice. USDA funding full time research at Tufts University to make this available to humans. Age Reversal Network will assist to develop this test of senolytic therapy efficacy for upcoming clinical trials. (September 8, 2021) When available, this test will enable precise dosing of senolytic drugs and nutrients. https://www.cell.com/cell-metabolism/pdf/S1550-4131(21)00115-7.pdf
  • 112. SIRT6 overexpression extends lifespan in mice Mice genetically altered to express more SIRT6 protein showed: • Median lifespan extension: 27% in males; 15% in females • Maximum lifespan extension: 11% in males, 15% in females (Confirms a 2012 study result) Roichman A. et al. Restoration of energy homeostasis by SIRT6 extends healthy lifespan. Nature Communications. 2021 May 28;12(1):3208. doi: 10.1038/s41467-021-23545-7. PMID 34050173 May 28, 2021
  • 113. Can we raise SIRT6 now? • Some fatty acids can increase SIRT6 function1 • Olive & other oleic acid oils1 • Fasting might help1 • Dietary cyanidins in red, purple, and blue fruits and vegetables might enhance function2 References 1. Feldman J. et al. Activation of the Protein Deacetylase SIRT6 by Long-chain Fatty Acids and Widespread Deacylation by Mammalian Sirtuins. J Biol Chem. 2013 Oct 25; 288(43): 31350–31356. doi: 10.1074/jbc.C113.511261. PMID 24052263. 2. Klein M. & Denu J. Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators. J Biol Chem. 2020 Aug 7; 295(32): 11021–11041. doi: 10.1074/jbc.REV120.011438. PMID 32518153.
  • 114. https://my.clevelandclinic.org/health/diseases/17855-amyloidosis-attr What is amyloidosis? Amyloidosis is a protein misfolding disorder. It causes proteins in the body to change shape (misfold), bind together and form amyloid deposits that damage tissues. Transthyretin amyloidosis begins as excess transthyretin proteins from the liver break apart and form amyloid fibrils that damage the heart, nerves and other tissues.
  • 115.  Transthyretin amyloidosis is caused by the accumulation of misfolded transthyretin proteins.  Misfolded transthyretin amyloid proteins build up and cause heart failure and other diseases.  If left untreated death occurs in 2 to 5 years. CRISPR/Cas9 gene editing reduced serum levels of transthyretin, a key biomarker for the disease, by 87% in humans. (Standard care therapy typically reduces transthyretin by 80%.) First Human Trial Using CRISPR June 26, 2021 https://www.fiercebiotech.com/biotech/first-human-trial-results-intellia-shows-world-gene-editing-has-arrived This is the first-time gene editing has been proven to work in humans, which “opens up a whole new area of therapies for patients that wasn't there.”
  • 116. “The U.S. Military Is Testing a Pill That Could Delay Aging” • U.S. Special Operations Command investing more money in anti-aging clinical trials. • Trial to start soon of “anti-aging pill” • NAD+ precursor being tested to enable “improved human performance…like increased endurance and faster recovery from injury.” July 6th, 2021 https://www.popularmechanics.com/science/health/a36905562/us-military-testing-anti-aging-pill/ “Reduced levels of NAD+ are linked to aging and numerous diseases, including mitochondrial dysfunction, inflammation and a variety of associated diseases. These levels decline as humans age and remain depleted during disease states.”
  • 117. NAD+ Restoration Turned Real 7 Years Ago • Since 2001, Life Extension® has sought ways to restore NAD+. • NAD+ helps turn “off” degenerative processes. • Proven methods to boost NAD+ became available in circa 2014. November 2014
  • 118. At age 50, we have 50% less cell NAD+ than age 20. By age 80, NAD+ levels drop as much as 98%. NAD+ Sharply Plummets with Age
  • 119. “We show that a slowdown in aging that increases life expectancy by 1 year is worth US $38 trillion, and by 10 years, US $367 trillion.” (These estimates are for the United States only.) July 5, 2021
  • 120. July 16th 2021 Scientists are demystifying aging — funding could add decades to our live BY MATT KAEBERLEIN, OPINION CONTRIBUTOR — 07/16/21 12:01 PM EDT https://thehill.com/opinion/healthcare/563337-scientists-are-demystifying-aging-funding-could-add-decades-to-our-lives?rl=1 $6.5 billion proposed in Federal funding for “geroscience” research “Over the past two decades, scientists have learned a great deal about the biology of aging. At the same time, we are also learning how to tweak those processes to slow, or even partially reverse, many of the functional declines that go along with old age.”
  • 121. September 6, 20181 1. https://www.elevian.com/blog-all/2018/9/15/business-insider-a-harvard-backed-drug-company-is-trying-to-develop-medicine-to-treat-and-prevent-aging-related-diseases 2. https://www.elevian.com/ + = Bringing GDF11 to Humanity August 12, 20212 $20 Million additional capital raised + $20 Million more when First Patient is dosed in Phase 1 Clinical Trial using recombinant GDF11
  • 122. Clinical applications of GDF11 in addition to potential systemic Age Reversal https://www.elevian.com/#elevian-pipeline
  • 123. August 21, 2021 Longevity investor Sergey Young is on a mission to extend people’s healthy lifespans – and knows exactly how it can be done. Sergey Young: 'Living to 150 or 200 years old will be as simple as getting vaccinated today' “Sergey Young, a venture capitalist who runs the Longevity Vision Fund, invests in health- tech companies promising to defeat aging, AI, Quantum computing, gene editing, the microbiome and more.” https://www.telegraph.co.uk/health-fitness/body/would-really-like-live-200/
  • 124. Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice September 3, 2021 Vertebral disc degeneration is prevalent in elderly people: leading cause of chronic back pain and disability. Systemic administration of dasatinib and quercetin prevented age-dependent progression of disk degeneration in mice. Potential benefits of D + Q treatment include alleviation of disc degeneration, reduction in systemic inflammation and improved physical condition during aging. https://www.nature.com/articles/s41467-021-25453-2
  • 125. September 2021 Prevention Magazine favorably describes:  Intermittent Fasting  Metformin  DNA methylation testing  Sirtuin activation  Young plasma transfer  Senolytic drugs RAADfest presented these years ago. (Prevention Magazine initially hostile to anti-aging medicine.)
  • 126. Rewriting the Rules of Biology  Time-honored doctrine of biology was that the fate of cells was irreversibly determined, and that rejuvenation was impossible.  Starting in 2006, cell reprograming demonstrated cellular rejuvenation.  Rejuvenation achieved in cells from very old humans (2011).  Research underway to rejuvenate whole organisms (including humans).  The “impossible” was achieved overnight via cellular reprograming. https://pubmed.ncbi.nlm.nih.gov/33627519 Cellular Reprograming
  • 127. Conveying the Message of Biological Rejuvenation  Human fate was inescapable: grow old and die!  Biological rejuvenation called impossible.  <20 years (blink of eye in evolutionary terms) that fatalistic view became obsolete.  Technology has turned cell rejuvenation (age-reversal) real.  In vivo autologous induced pluripotent stem cell research may begin 2022. Think of how fortunate we are…to live in a time of these marvelous achievements…a time in which rejuvenation and indefinite life extension is within our reach.
  • 128. February 28, 2021  This 2021 published review and additional investigations summarize age-reversal impact of cell reprograming.  Human trials being investigated.  Funded by Bill Faloon and other charitable donors. https://pubmed.ncbi.nlm.nih.gov/33627519 “When cells were reprogrammed with a 6- transcription factor cocktail the (degenerative) alterations were fully reversed and cells fully rejuvenated.”
  • 129. Carnegie Mellon’s Cloud Lab to Automate Labor-Intensive Science Exp August 31, 2021 • $40 million laboratory designed to automate lab experiments with robotics and artificial intelligence. • Experiments carried out remotely by about 200 different types of AI robotic machines. • Scientists from around the world can synthesize, or create, molecules using a robot based in Switzerland. “The benefit comes in accelerating science” https://www.wsj.com/articles/carnegie-mellons-cloud-lab-to-automate-labor-intensive-science-experiments-11630348526?mod=searchresults_pos2&page=1 Sept 4, 2021 “…Silicon Valley’s latest wild bet on living forever” https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/
  • 130. Sept. 4, 2021 “Meet Altos Labs, Silicon Valley’s latest wild bet on living forever” https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/ New anti-aging company funded by Jeff Bezos and others to pursue cellular reprogramming to revitalize entire animal bodies and eventually humans. Recruiting large cadre of university scientists with lavish salaries and promise they can pursue unfettered blue-sky research on how cells age and how to reverse that process. Altos will fund researchers such as Steve Horvath (ULCA inventor of DNA methylation testing) and Shinya Yamanaka (shared 2012 Nobel Price using “Yamanaka Factors” to reprogram cells).
  • 131. September 5, 2021 •The two are funding Altos Labs, which is looking to develop anti-aging techniques •Among the expertise being brought on include those who have looked extensively in cell reprogramming •The technique reverts cells back into their stem cell state, which while dangerous, can be used to reverse aging •The technique was first discovered by Dr. Shinya Yamanaka, who will serve as an advisor to the company https://www.dailymail.co.uk/news/article-9960175/Jeff-Bezos-Yuri-Milner-fund-anti-aging-start-up.htm Jeff Bezos and Yuri Milner 'fund anti-aging start-up aimed at biological reprogramming which could help humans live FOREVER'
  • 132. Yamanaka Factors Potential Systemic Regeneration using Induced Pluripotent Stem Cell Therapy Cellular (Induced Pluripotent Stem Cells) Induced Pluripotent Stem Cell-based Therapy iPSC-derived progenitor cells Old fibroblasts reprogrammed into autologous induced pluripotent stem/progenitor cells Cellular Reprogramming adding NANOG + LIN28 Elderly Purification of induced progenitors to remove non-differentiated iPSCs
  • 133. What’s Transpired Since RAADfest 2020? October 2020 to October 2021 Reaching the Critical Mass: the minimum size or amount of something required to start or maintain a venture. Consensus advancing to the “I get it moment” as it relates to prospect of age reversal.
  • 134. “Epigenetic rejuvenation seems to hold the key to arresting or even reversing organismal aging.” February 28, 2021 FUNDING The work from our laboratory is supported in part by grants # MRCF 7-25-19 from the Medical Research Charitable Foundation and the Society for Experimental Gerontological Research, New Zealand, by a grant from Betterhumans Inc., Florida, USA and grant #PICT18-00907 from the Argentinian Agency for the Promotion of Science and Technology to RGG. https://pubmed.ncbi.nlm.nih.gov/33627519/
  • 135. “Rejuvenation has already been achieved in old human and animal cells. Eight independent studies show that different cell types from old humans and mice can be rejuvenated by cell reprogramming. Achieving the same in humans will be just a matter of improving our technology.” Email from Rodolfo Goya, Ph.D. to Bill Faloon - August 5, 2021
  • 137. https://www.nejm.org/doi/full/10.1056/NEJMra1905136 EffectsofIntermittentFastingonHealth,Aging,andDisease Suppresses inflammation Reduces obesity and type II diabetes Protects against cardiovascular disease Lowers risk of neurodegenerative disorders Reduces cancer incidence Animal models show consistent robust benefits of intermittent fasting: Dec. 26, 2019
  • 138. https://www.nejm.org/doi/full/10.1056/NEJMra1905136 Human studies show intermittent fasting ameliorates: Dec. 26, 2019  Obesity  Dyslipidemia  Hypertension  Inflammation  Insulin resistance Effects of Intermittent Fasting on Disease Risk Markers
  • 139. natureresearch October 27, 2020 Scientific Reports | (2020) 10:18341 | https://doi.org/10.1038/s41598-020-73767-w “Intermittent fasting from dawn to sunset for 4 consecutive weeks induces anticancer serum proteome response & improves metabolic syndrome” No eating/drinking between dawn and dusk…14-15 hours each day: • 7.25 pounds of weight loss • 8.8 mmHg reduction in blood pressure • Significant increase in tumor suppressor/anticancer proteins • Significant decrease in several tumor promoter/pro-cancer proteins • Increasing a protein called calreticulin (by around 16 times) • Calreticulin enhances IgG response to a SARS-CoV spike protein
  • 140. “In the multi-variable model, high adherence to the Mediterranean diet was associated with 25% lower risk of death as compared with the lowest category.” https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/mediterranean-diet-and-mortality-in-the-elderly-a-prospective-cohort-study-and-a- metaanalysis/F2D6B083AA187849477112DB77820521 “Mediterranean diet and mortality in the elderly: a prospective cohort study and a meta-analysis” Published online by Cambridge University Press: 30 August 2018
  • 141. June 30, 2021 Mediterranean Diet Score, Dietary Patterns and Risk of Sudden Cardiac Death Study of 21,000 people over 9.8 years reveals:  Diet high in fried foods, organ meats and processed meats regularly had a 46% higher risk of sudden cardiac death compared to those with least adherence.  Those who most closely followed the traditional Mediterranean diet had a 26% lower risk of sudden cardiac death than those with the least adherence to this eating style. Originally published 30 Jun 2021https://doi.org/10.1161/JAHA.120.019158 Journal of the American Heart Association. ;0:e019158 Mediterranean diet defined as high in vegetables and whole grains, low intake of meat, high intake of marine omega-3s.
  • 142. May 2008 Sept 2016 April 2015 Longevity Benefits of Mediterranean Diet
  • 143. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801 Mediterranean Diet Healthy Foods More fruits, vegetables, and whole grains, and less dairy & meat than typical Western diet.
  • 144. Foods to Reduce or Avoid Re  Red meat  Overcooked meats  Processed red meat (hot dogs, bacon)  Butter  Cured ham (nitrite/nitrite preserved meats)  Most frozen meals  Soda, desserts, candy  Most processed foods  Sugars  Refined grains (white bread/white grain pasta)  Excess salt https://www.foodnetwork.com/healthy/articles/what-foods-are-not-allowed-on-mediterranean-diet
  • 145. Baron Benjamin de Rothschild, heir to a French banking fortune, died of a heart attack at age 57 on January 15, 2021. He oversaw the Edmond de Rothschild empire, which has stakes in banks in France and Switzerland, owns restaurants and hotels vineyards in Argentina, New Zealand, South Africa, Spain and France. Who missed the longevity boat? Baron Benjamin de Rothschild (1963 - 2021) Expiration date: Jan. 15, 2021 net worth > $1.5 billion https://www.forbes.com/profile/benjamin-de-rothschild/?sh=401323666454
  • 146. Age-standardized death rate rate from heart disease per 100,000 people dropped: Reduction in Heart Disease Mortality in the United States 68% decline over 45 years From: 520 in 1969 To: 167 in 2014
  • 147. Average American Died under age 70 in 1960 How to add 4.7 Years to Your Life Expectancy
  • 148. The Omega-3-Index is a blood test that can measure the percent of omega-3 fatty acids in red blood cells. Red blood cell EPA/DHA content is a good measure of sustained omega-3 status. You want your Omega-3-Index score to be > 6.8% Typical Japanese Omega-3-Index is > 8.0% that may correlate with 5 year longer life expectancy in Japan.
  • 149. Journal of Clinical Lipidology (2018) 12, 718-727 https://doi.org/10.1016/j.jacl.2018.02.010 People with omega-3 RBC scores > 6.8% compared with those < 4.2% : 39% lower risk for cardiovascular disease 34% lower risk of death from any cause (Subjects average age 66 and followed over 7 years) Higher Omega-3 Index associated with reduced risks because of: 1) Lowering of triglycerides, blood pressure, platelet aggregation, heart rate 2) Lower markers of inflammation and arterial plaque vulnerability 3) Reduced rate of telomere length attrition December 2018 Omega-3-Index and Risk of Death
  • 150. June 16th, 2021 The American Journal of Clinical Nutrition, nqab195, https://doi.org/10.1093/ajcn/nqab195  Predictive model for correlation/association from Framingham Offspring Cohort (n= 2,240)  Baseline omega-3-Index score and relevant covariates evaluated over 11-year follow-up.  Standard risk adjustments: age, sex, total cholesterol, HDL cholesterol, hypertension treatment, systolic blood pressure, smoking status, prevalent diabetes.  Extensive validation process to account for confounding risk factors Analysis reveals red blood cell omega-3 index over 6.8% in people is associated with 4.7 years additional life expectancy compared with omega-3 index under 4.2%. Higher Omega-3 Blood Score = Nearly 5 years increased Life Expectancy
  • 151. July 27, 2021 Omega-3-Index scores in Life Extension® Supporters  Only 1,300 mg of added EPA/DHA from fish/supplements moves Omega-3-Index from <4.2% to >6.8%  Plant derived omega-3 precursors (ALA) not shown to achieve these robust EPA/DHA increases.  Omega-3-Index at-home test costs $79 --- May save $$$ on fish oil supplements.  Omega-3-Index test available at: www.LifeExtension.com/blood Journal of Clinical Lipidology (2018) 12, 718-727 https://doi.org/10.1016/j.jacl.2018.02.010
  • 152. Bridging the Longevity Gap Urgent Need to Access Age-Reversal Interventions
  • 153.
  • 154. Sheldon G. Adelson, a cabdriver’s son who built the world’s largest empire of casinos and resort hotels in Las Vegas, Macau, Singapore and other gambling meccas. The cause was complications of non-Hodgkin’s lymphoma. Donated to many charities including some that supported medical research. Who missed the longevity boat? Sheldon Adelson (1933 - 2021) Expiration date: Jan. 11, 2021 net worth > $35.8 billion https://www.palmerfuneralhomes.com/obituary/Arthur-Decio
  • 155. Stephen Bechtel Jr. led the Bechtel construction empire for 30 years. The Stanford-educated engineer became a billionaire while leading BECHTEL’s expansion through “mega-projects” in Saudi Arabia, the U.S. and Canada. Who missed the longevity boat? Stephen Bechtel Jr. (1925- 2021) Expiration date: Mar. 15, 2021 Net worth > $3.5 billion https://www.bloomberg.com/news/articles/2021-03-16/stephen-bechtel-jr-heir-who-expanded-bechtel-group-dies-at-95
  • 156. Who missed the longevity boat? John C. Martin (1951 - 2021) Expiration date: Mar. 30, 2021 Net worth > $1.2 billion https://www.fiercepharma.com/pharma/longtime-gilead-captain-john-martin-mastermind-life-saving-hiv-hcv-drugs-has-died Credited for turning Gilead into $100 billion biotech giant. Gilead developed a cure (Sovaldi®) for 95% of hepatitis C. Died after apparent fall while walking home in Palo Alto. “He was always driving us to do better.” quoted Gilead executive
  • 157. Risk of Delaying Human Research Chronic Diseases May Negate Regenerative Benefits
  • 158. July 14 ,2021 “Brain Implant Lets Man ‘Speak’ After Being Silent for More Than a Decade” New England Journal of Medicine study shows brain implant in a stroke paralyzed (15 years) patient enabled brain signals to be translated into words on a computer screen. https://www.nejm.org/doi/full/10.1056/NEJMoa2027540 Comment by expert on brain-computer interfacing: Human Brain/Cloud Interface technologies will empower us to preserve crucial brain information, interface our brain directly with the cloud, positively impact learning, and provide data for the study of consciousness. This technology is not distant in the future, as many believe. Nuno R.B. Martins, Ph.D. (July 28, 2021)
  • 159. https://www.sciencedaily.com/releases/2019/03/190325120339.htm March 29, 2019 Human Brain/Cloud Interface Human brains could be connected to the internet in 'next few decades,' scientists predict
  • 160. https://www.foxnews.com/science/human-brains-connected-internet-scientists-predict April 15, 2019 "These devices would navigate the human vasculature, cross the blood-brain barrier, and precisely autoposition themselves among, or even within brain cells," the study's senior author, Robert Freitas, Jr., said. "They would then wirelessly transmit encoded information to and from a cloud-based supercomputer network for real-time brain- state monitoring and data extraction." MANKIND COULD HAVE ELECTRIC IMMORTALITY BY 2050 Human brains could be connected to the internet in 'next few decades,' scientists predict
  • 161. https://medicalxpress.com/news/2019-04-future-human-braincloud-interface-people.html A future 'human brain/cloud interface' will give people instant access to vast knowledge via thought alone April 12, 2019 An international collaboration led by researchers at UC Berkeley and the US Institute for Molecular Manufacturing predicts that exponential progress in nanotechnology, nanomedicine, AI, and computation will lead this century to the development of a "Human Brain/Cloud Interface", that connects brain cells to vast cloud-computing networks in real time.
  • 162. Dr. Nuno Martins published paper Human Brain/Cloud Interface has attracted enormous attention. Here is data from Frontiers of Neuroscience website: More views than 90% of all “frontiers” articles https://www.frontiersin.org/articles/10.3389/fnins.2019.00112/full Significant relevance in neuroscience community. Frontiers in Neuroscience is world's most-cited journal in the neurosciences field. (There are 67 “frontiers” journals.) Human Brain/Cloud Interface paper has more views than 90% of ALL Frontiers articles. Once this concept reaches critical mass…someone will likely make it happen. March 29, 2019
  • 163. Elon Musk’s Brain Computer Startup Raises $205 Million from Google Ventures & Others • Neurolink is trying to develop high-bandwidth brain implants that can communicate with phones and computers • Total investment in the company now stands at $363 million. July 30th, 2021 https://www.cnbc.com/2021/07/30/elon-musks-neuralink-backed-by-google-ventures-peter-thiel-sam-altman.html
  • 164. • Survive until year 2045. • Singularity enables neocortex to merge with cloud-based artificial intelligence. • Neocortex/AI enters limitless self- improvement cycles. Result is super-intelligence that advances our abilities to incomprehensive levels Ray Kurzweil’s Exit Plan to Immortality
  • 165. December 17, 1903 First flight: 120 feet/20 feet off ground
  • 167. December 20, 1957 Intercontinental Air Travel 54 Years after Wright Brothers first in flight
  • 169. 1903 2021 Exponential Advances in only 118 Years April 9, 2021
  • 170. 1903 - First “Flying Machine” travels 120 feet at Kitty Hawk 2021 - Robot + helicopter travel 140 million miles to Mars 2011- Cells from 100-year-old human fully rejuvenated1 2022 – Autologous iPSC studied for systemic rejuvenation 118 Years Later 11 Years Later 1. https://pubmed.ncbi.nlm.nih.gov/22056670/
  • 171. 1903 - First “Flying Machine” travels 120 feet 2021 - Robot + helicopter travel 140 million miles to Mars 1997- Longest lived human (J.Calment) dies at age 122 (118 Years Later) What if Human Lifespans increase at same rate as Aviation/Space Travel? 2045(?) – Escape velocity yields 739-billion-year lifespans https://www.youtube.com/watch?v=BPKHHQFI-WM
  • 172. • Old Fibroblasts + Yamanaka-like factors = Autologous Pluripotent Cells • Remove senescent cells from bone marrow niche. • Repopulate bone marrow niche with autologous hematopoietic and mesenchymal stem cells. • Hematopoietic stem cells reverse immune senescence and anemia without “graft vs host” concerns because genetic profile virtually identical to host. • Mesenchymal stem cells systemically regenerate tissues. • Study objective: Systemic age-reversal + immune restoration in humans. Recap of Human Age Reversal Research Initiative (Large animal pilot studies will first evaluate safety and regenerative efficacy)
  • 173. B. Wayne Hughes, co-founder of largest self-storage company. Founded in 1972 with $50,000. Public Storage value: $56 billion. Donated money to cancer research. Dead at age 87. Who missed the longevity boat? B. Wayne Hughes (1933 - 2021) Expiration date: Aug, 18, 2021 net worth > $4.1 billion https://www.forbes.com/sites/michelatindera/2021/08/18/b-wayne-hughes-billionaire-founder-of-public-storage-dies-at- 87/?sh=17193a5f42fe
  • 174. Apple News - July 11, 2021 “Can Science Cure Death? It Sure Looks Like It” “The World Health Organization added a distinction that characterizes aging as a disease.” https://apple.news/A4LOishZsQQ2xGEgHrlSCxA “Saraev, like any number of young optimistic tech-associated men believes that if he takes the correct preventative steps now, he might well live forever.”
  • 175. Carnegie Mellon’s Cloud Lab to Automate Labor-Intensive Science Exp August 31, 2021 • $40 million laboratory designed to automate lab experiments with robotics and artificial intelligence. • Experiments carried out remotely by about 200 different types of AI robotic machines. • Scientists from around the world can synthesize, or create, molecules using a robot based in Switzerland. “The benefit comes in accelerating science” https://www.wsj.com/articles/carnegie-mellons-cloud-lab-to-automate-labor-intensive-science-experiments-11630348526?mod=searchresults_pos2&page=1 Sept 4, 2021 “…Silicon Valley’s latest wild bet on living forever” https://www.technologyreview.com/2021/09/04/1034364/altos-labs-silicon-valleys-jeff-bezos-milner-bet-living-forever/
  • 176. World’s Largest Anti-Aging Organization https://www.lifeextension.com/about/life-extension-story/history  First to introduce DHEA to delay systemic aging (1981)  First to introduce aspirin to prevent heart attack (1983)  First to introduce coenzyme Q10 to reverse heart failure (1983)  First to introduce cimetidine as adjuvant cancer therapy (1986)  First to introduce melatonin to improve immune function (1992
  • 178. Unparalleled Track Record of Biomedical Innovation Established 1977
  • 179. Copyright ©Life Extension®. Confidential and proprietary. How I Fund Age Reversal Research Supplement Sales Support Rejuvenation Projects
  • 181. 181 “They’re not fond of rules. And they have no respect for the status quo.” “You can’t ignore them. Because they change things. They push the human race forward.” “People who are crazy enough to think they can change the world, are the ones who do.” Steve Jobs Excerpts from “Think Different” campaign 1997
  • 182. Prospect of Human Age Reversal William Faloon RAADFest October 2nd, 2021