Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
Interventions Designed to
Reverse Human Aging

Age Reversal
Interventions
Autophagy Plasma exchange
Remove
senescent cells
Combat
Immune senescence
Lengthen
telomeres
AMPK/
mTOR
NAD+
Exosomes

The Nobel Prize in Physiology or Medicine 2012
These transcription factors are called:
“Yamanaka Factors”
Four specific genes encode transcription
factors that can convert somatic cells
into pluripotent stem cells that can
propagate indefinitely.
nobelprize.org/prizes/medicine/2012/yamanaka

These 'induced pluripotent stem
cells,' or iPS cells, are made from
a patient's skin or blood.
Researchers have found a
way to roll back the clock on
adult cells, allowing them to
behave much like stem cells
from embryos do.
MakingOldCellsNewAgain

Cells are collected
Adult skin or blood cells
are used to create iPS cells.
In Aspen Neuroscience's
method, tissue is taken from
the skin. The skin or blood cells
are cultured in petri dishes.
Step 1:
Source: Aspen Neuroscience; Kapil Bharti, National Institutes
of Health; Kevin Hand/THE WALL STREET JOURNAL

Kick-startingthechange
Proteins called Yamanaka
factors are added, either
directly or using harmless
viruses that carry genes to
create the proteins.
Step 2:
Source: Aspen Neuroscience; Kapil Bharti, National Institutes
of Health; Kevin Hand/THE WALL STREET JOURNAL

Conversiontostemcells
The Yamanaka factors
take the cells to an
embryonic-like state.
Step 3:
These cells are then grown
into colonies of stem cells.
Source: Aspen Neuroscience; Kapil Bharti, National Institutes
of Health; Kevin Hand/THE WALL STREET JOURNAL

Makingspecializedcells
Stem cells are doused
with reagents to mimic
the environment for
specific cells in a fetus.
Step 4:
Theythencan becomecomplex
tissues, such as brain cells.
Source: Aspen Neuroscience; Kapil Bharti, National Institutes
of Health; Kevin Hand/THE WALL STREET JOURNAL

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
Rapamycin

60%
(in middle-aged mice)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/

“In middle-aged mice, just 3 months of high-dose rapamycin
treatment was sufficient to increase life expectancy up to 60%.
When taken late in life, rapamycin increases lifespan by 9-14%
[155], despite the dosage being suboptimal. This possibly equates
to more than 7 years of human life.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/

Long-lasting geroprotection from brief rapamycin treatment in
early adulthood by persistently increased intestinal autophagy
Geroprotection obtained with brief pulse dose in female fruit flies/mice.
Brief rapamycin treatment in early adulthood extended lifespan.
Early adulthood treatment induced long-term increase in autophagy.
Intestinal improvements maintained 6 months after rapamycin withdrawn (mice).
https://www.nature.com/articles/s43587-022-00278-w
August 29, 2022
“The licensed drug rapamycin has potential
to be repurposed for geroprotection.”

Slash Cancer Risk, Reduce Belly Fat
Rapamycin inhibits mTOR and has been
shown to increase lifespan in animals.
Rapamycin reduces cancer risk by 40%
in human kidney transplant patients.
Research indicates rapamycin reduces
visceral fat in non-transplant patients.
Turn back mTOR
Turn back the clock

IncreasedFidelityofProteinSynthesisExtendsLifespan
The paper’s authors emphasize that the baseline
rate of error in protein synthesis can be hundreds of
thousands of times more then the DNA mutation
rate. Making it a major neglected aspect of aging.
https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00417-4
“Weshowthatanti-agingdrugssuchasrapamycin,
Torin1,and trametinibreducetranslationerrors,
and that rapamycin extends further organismal
longevity in RPS23 hyper-accuracy mutants. This
implies a unified mode of action for diverse
pharmacological anti-aging therapies.”
November 2,2021

March 28, 2017
Rapamycin (sirolimus) increased
elderly people’s response to flu
vaccines by 20%.
This has led to research if rapamycin a
drug can slow or reverse the
symptoms of old age.
https://www.technologyreview.com/s/603997/is-this-the-anti-aging-pill-weve-all-been-waiting-for/
“Can a pill make you younger?”

NIH Funds $23 Million
Dog Study that includes
RAPAMYCIN Daniel Promislow
principal investigator of the Dog Aging Project
“Old dogs, new tricks: 10,000
pets needed for aging study”
https://www.nbcnews.com/health/health-news/old-dogs-new-tricks-10-000-pets-needed-science-n1082151

PNAS October 15, 2019 116 (42) 20817-20819; first published September 30, 2019
https://doi.org/10.1073/pnas.1913212116
Rapamycin Lithium Trametinib
+ +
Fruit Fly Lifespan Extension by 48%
=
“…a combination of drugs already approved for
human use is a viable strategy to maximize animal
longevity…”
This study supports the stairstep approach advocated to enable us to live significantly longer
Oct 15. 2019

Fruit flies received drugs separately and/or in combination.
 Each drug individually extended lifespan by 11%
 Pairing two drugs extended lifespan roughly 30%
 Three drugs combined extended lifespan by 48%
Castillo-Quan, Jorge Iván, Luke S. Tain, Kerri J. Kinghorn, Li Li, Sebastian Grönke, Yvonne Hinze, T. Keith Blackwell, Ivana
Bjedov, and Linda Partridge. "A triple drug combination targeting components of the nutrient-sensing network
maximizes longevity." Proceedings of the National Academy of Sciences 116, no. 42 (2019): 20817-20819.
Combination Treatments Are Essential
Oct 15. 2019

Compound Combinations Targeting
Longevity: Challenges and Perspectives
“Anti-aging drug therapy is one of the most
promising strategies to combat aging.”
“Aging is currently at the top of the major global concerns,
urgently requiring effective, large-scale interventions to decrease
the number of late-life disorders and improve human healthspan.”
“There is a great rationale for use of
combinations of anti-aging interventions”
“Most geroprotective compounds affect
only a few biological targets”
https://pubmed.ncbi.nlm.nih.gov/36642188/
Jan. 13th, 2023

March 5th, 2022 National Institutes of Health - Clinicaltrials.gov listed study
Rapamycin Human Study Receives $485,000 Funding
Sponsor: AgelessRx Collaborator: University of California,
Los Angeles
Principal investigators: James Watson, M.D. and Sajad Zalzala, M.D.
|
► 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.
► > 50 people enrolled at $360 each (original cost before donations was $1,200).

Aging (Albany NY). 2019 Oct 15; 11(19): 8048–8067.
Published online 2019 Oct 4. doi: 10.18632/aging.102355
PMCID: PMC6814615
PMID: 31586989
Rapamycin for longevity: opinion article
Mikhail V. Blagosklonny 1
Author information Article notes Copyright and License information Disclaimer
Go to:
Abstract
From the dawn of civilization, humanity has dreamed of immortality. So why didn’t the discovery of the anti-aging properties
of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side
effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as
anti-aging drugs today. Furthermore, the alternative to the reversible (and avoidable) side effects of rapamycin/everolimus
are the irreversible (and inevitable) effects of aging: cancer, stroke, infarction, blindness and premature death. I will also
discuss why it is more dangerous not to use anti-aging drugs than to use them and how rapamycin-based drug combinations
have already been implemented for potential life extension in humans. If you read this article from the very beginning to its
end, you may realize that the time is now.
Rapamycin for longevity: opinion article
“it is more dangerous not to use
anti-aging drugs than to use them”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
Senolytics

Senescent cells accumulate with normal aging and:
Removing Senescent Cells Confers Healthy Longevity

Senolytics are compounds
that selectively destroy
senescent cells.

320 papers for
2022 alone
“Senolytics”
Publications increase
from near zero in 2013
to 956 by close of 2022.
https://pubmed.ncbi.nlm.nih.gov/?term=senolytic
Search of the National Library of Medicine Website
Dec. 31st, 2022 |

Oct.13,2021
https://www.nature.com/articles/s41598-021-99852-2
Highly selective marker of cellular
senescence present on membranes
of senescent cells targets specific
delivery of senolytic drugs into
senescent cells.
nature
“Non-senescent cells were not affected by either antibody,
confirming the specificity of the treatment. …”
A Vaccine to Eliminate Senescent Cells!

A Vaccine Eliminates Senescent Cells
https://www.longevity.technology/a-vaccine-for-aging-that-eliminates-senescent-cells
Dec. 13, 2021

Senolytics described in new book.
https://medium.com/@bdajess/drug-that-increases-human-lifespan-to-200-years-is-in-the-works-edb3a1a64af1
“A fascinating look at how scientists
are working to help doctors treat the
aging process itself, helping us all to
lead longer, healthier lives.”
— Sanjay Gupta, MD
“I don’t think there is any kind of
absolute cap on how long we can live.”
— Dr. Andrew Steel
British Computational Biologist

https://www.the-scientist.com/features/can-destroying-senescent-cells-treat-age-related-disease--67136
Can Destroying Senescent
Cells Treat Age-Related Disease?
A handful ofclinical trials are underway to find out whether
drugs that target senescent cells can slow the ravages of old age.
March 1st, 2020
Several biotechs have sprouted in recent years to identify
compounds that target senescent cells and put such
“senolytic” drugs to the test in humans—efforts that are
supported by considerable funding influxes from both
federal sources like the NIH and private sources such as that
of Peter Theil and Jeff Bezos.
“Getting rid of senescent cells is enough to effectively rejuvenate
ananimal—thattellsyouthey’reareallyimportantdriverofaging.”

Buck Institute Announces Non-Invasive
Test to Measure Senolytic Efficacy
JUNE1,2021
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.
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

November 09, 2021 | DOI:https://doi.org/10.1016/j.mayocp.2021.06.025
Nov. 09, 2021
In a study comparing the effectiveness of 2 different senolytics:
Dasatinib caused 10.56 pounds more weight loss, reduced
hemoglobin A1c by 0.80% more and reduced serum glucose
levels by 43.7 mg/dL more then Imatinib, a different senolytic.
“This hemoglobin A1c decrease is quantitatively comparable
to that which occurs with the use of hypoglycemic agents
commonly used as first-line agents, such as metformin.”

November 09, 2021 | DOI:https://doi.org/10.1016/j.mayocp.2021.06.025
Nov. 09, 2021
Of note, 2 of 4 insulin-
dependent patients in
the dasatinib group no
longer required any
insulin. Compared with
1 of 9 insulin-dependent
patients in the imatinib
group.

November 09, 2021 | DOI:https://doi.org/10.1016/j.mayocp.2021.06.025
Nov. 09, 2021
“Dasatinib may have
antidiabetic effects
comparable tocontemporary
diabetic treatments andmay
be considered for use as a
novel diabetic therapy.”
Conclusion: A Cause of Age-associated Disease(s) like Diabetes

 Improvefrailtysymptoms(gait,gripstrength)
 Improve kidney/liver pathologic age scores
 Improve cardiac/arterial function
 Decrease osteoporosis
 Increase exercise endurance
 Enhance coat color appearance
 Reduce tremors and urinary incontinence
 Extend healthy lifespan
Results of Quercetin + Dasatinib in Rodents
Zhu, Yi, Tamara Tchkonia, Tamar Pirtskhalava, Adam C. Gower, Husheng Ding, Nino Giorgadze, Allyson K. Palmer et
al. "The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs." Aging cell 14, no. 4 (2015): 644-658.

Karin, Omer, Amit Agrawal, Ziv Porat, Valery Krizhanovsky, and Uri Alon. "Senescent cell turnover slows with
age providing an explanation for the Gompertz law." Nature communications 10, no. 1 (2019): 1-9.
Shi, Qiang, Keiko Aida, John L. Vandeberg, and Xing Li Wang. "Passage-dependent changes in baboon
endothelial cells—relevance to in vitro aging." DNA and cell biology 23, no. 8 (2004): 502-509.
Senescent Cells Snowball
“Senescent cells (SnCs) produce and secrete various
bioactive molecules including interleukins, growth
factors, matrix-degrading enzymes and reactive oxygen
species… continuous exposure to SnCs induced cell
senescence in intact bystander fibroblasts.”
"(i) SnC production rate increases with age due to accumulation
of mutations, telomere damage, and other factors that trigger
cellular senescence, (ii) SnCs catalyze their own production by
paracrine and bystander effects, (iii) SnC removal decreases with
age due to age-related decline in immune surveillance
functions, and (iv) SnCs reduce their own removal rate…”

The Burden is Eventually Unbearable
Senescent cell’s turnover in 5 days in 3-month-old
mice but take 25 days in 22-month-old mice. This
model predicts a vicious cycle where senescent
cells accumulate faster and are degraded slower.
"Our results suggest that treatments that
remove senescent cells can have a double
benefit: an immediate benefit from a
reduced senescent cell load, and a longer-term
benefit from increased senescent cell removal."
At the point of ~30% SnC load animals often
appear to reach a tipping point resulting in death.
https://www.nature.com/articles/s41467-019-13192-4

Dr. Alan Green at his practice in Little Neck, NY
now has 500+ patients using rapamycin with
100+ patient adding dasatinib, fisetin and
quercetin .
Dr. Green’s Anti-Aging Cocktail
1) Rapamycin
2) Dasatinib
3) Fisetin
4) Quercetin
Now in Clinical Use:
https://senolyticstreatment.com/

Dr. Alan Green’s Senolytic Protocol
 Dasatinib: 100 mg a day for 3 days
 Quercetin: 1000 mg a day for 3 days
 Fisetin 1500 mg day for 3 days
https://senolyticstreatment.com/
These are MAXIMUM DOSES. Patients determine sensitivity with smaller doses.
For diseases like Alzheimer's, cardiomyopathy, pulmonary fibrosis, emphysema,
fatty liver, chronic kidney disease, metabolic syndrome, obesity, frailty:
1-2 of these senolytic treatments a month
For lifespan and healthspan: 4 treatments a year (3-month) interval
2020
INFO

Senolytics May Reverse Heart Failure
Clinical trial urgently needed!
Improve Survival
“Pharmacological clearance of senescent
cells improves survival and recovery in aged
mice following acute myocardial infarction”1
1. https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.12945

Normal Aged Mouse Senolytic Treated Mouse

Anti-Cancer Properties of Senolytics May. 17, 2019
https://science.sciencemag.org/content/364/6441/636.full
“Indeed, elimination of senescent
cells with aging attenuates tumor
formation in mice, raising the
possibility that senolysis might be an
effective strategy to treat cancer.”

8 Million Americans Suffer Chronic Heart Failure
Human Studies Urgently Needed!
Pharmacologic and genetic removal of p16-positive
(senescent) cells in mice appears to ameliorate (or
improve) the level of age-induced fibrosis and
hypertrophy in senescent cardiac muscle cells, and
may support regeneration of cardiomyocytes…
What we learned earlier studies:

“Aged‐senescent cells contribute to impaired heart regeneration.” Aging Cell; June 2019
Senescent Cells Damage Aging Hearts
“Aging leads to increased cellular
senescence and is associated with
decreased potency of tissue‐specific
stem/progenitor cells.”
“In aged subjects (>70 years old), over half
of cardiac progenitor cells are senescent…”
“Therapeutic approaches that eliminate senescent
cells may alleviate cardiac deterioration with aging
and restore the regenerative capacity of the heart.”

Deadly Impact of Senescent Cells
July 9, 2018
“Senolytics improve physical function and increase lifespan in old age.” Nature Medicine, July 9th, 2018
Transplanting small numbers of
senescent cells into young mice
causes:
1) Persistent physical dysfunction.
2) Spread of cell senescence to
host tissues.

Deadly Impact of Senescent Cells
July 9, 2018
“This indicates potency of senescent cells in shortening healthspan/lifespan.”
“Senolytics improve physical function and increase lifespan in old age.” Nature Medicine, July 9th, 2018
Transplanting senescent
cells into older mice
causes:
1) Same pathologies as
young mice.
2) Reduced survival.

Senolytics Increase Lifespan in Old Age
July 9, 2018
“Senolytics improve physical function and increase lifespan in old age.” Nature Medicine, July 9th, 2018
Dasatinib + quercetin selectively
eliminated senescent cells and
decreased secretion of frailty-
related pro-inflammatory cytokines
in human adipose explants.
“Our study provides proof-of-concept evidence that senescent cells can
cause physical dysfunction and decreased survival even in young mice,
while senolytics can enhance remaining health and lifespan in old mice.”

July 9, 2018
“Senolytics improve physical function and increase lifespan in old age.” Nature Medicine, July 9th, 2018
Intermittent oral administration of senolytics to senescent
cell-transplanted young mice and naturally aged mice:
Senolytics Increase Lifespan in Old Age
Alleviates physical dysfunction
Increases post-treatment survival by 36%

July 9, 2018
Magazine
“It’slooking like veryoldmice are able to substantially improve their health
span, reduce or delay age-related diseases and increase their survival.”
They calculated that if only one in 7,000 to 15,000 cells is senescent, then age-related
problems in physical function started to appear in the mice.
Like a contagion, senescent cells seem to pass on their accelerated aging abilities to healthy
cells by releasing a number of factors that can cause tissues like muscle to deteriorate.
Mice given senescent cells and the senolytic compounds lived 36% longer than animals
with senescent cell transplants who were not given the drugs.
How Scientists Are Testing
Cancer Drugs to Slow Down Aging
https://time.com/5333752/aging-drugs/

Probable Mechanism Of
Senolytics Against Osteoarthritis
►Remove senescent cells in joints.
►Macrophages clear dead senescent cells.
►Inflammation/protein degradation abates.
Chondrocytes Restore Joint Cartilage.

July 9, 2018
NAD+ human studies show osteoarthritis improvements.
Self-experimenters may consider NAD+ followed by senolytics.
 Remove senescent cells with dasatinib + quercetin.
 Increase sirtuin 6 (SIRT6) for chondrocytes to
regenerate cartilage.
 Resveratrol and NAD+ boosts SIRT6 expression.
Senolytics and NAD+ to
Reverse Osteoarthritis and Aging
Physician supervision advised

I. Damaging extracellular matrix
II. Inducing fibrosis
III. Inhibiting stem cell function
IV. Recruiting inflammatory immune cells
Senescentcellssecretetoxicsenescence
associatedsecretoryphenotype(SASP)
May. 17, 2019
https://science.sciencemag.org/content/364/6441/636.full
SASP accelerates aging by:

Anti-Cancer Properties of Senolytics May. 17, 2019
https://science.sciencemag.org/content/364/6441/636.full
“Indeed, elimination of
senescent cells with aging
attenuates tumor formation
in mice, raising the
possibility that senolysis
might be an effective
strategy to treat cancer.”

Example of Senolytic Age Delay
Normal aged mouse has
characteristic bent-spine,
cataracts, and loss of coat
fur (hair).
https://www.cnbc.com/2018/08/29/-jeff-bezos-is-backing-this-scientist-who-is-working-on-a-cure-for-aging.html
Same aged mouse from
senolytic-treated group
appears outwardly younger
and healthy.
Bent spine
Cataract
Same age mouse
looks much younger
Hair loss
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845101/
Untreated Senolytic Treated Starting at Mid-Age

Lifespan Increase in Senolytic-Treated Mice
Median lifespans increased 24% to 27%
https://www.cnbc.com/2018/08/29/-jeff-bezos-is-backing-this-scientist-who-is-working-on-a-cure-for-aging.html
Bent spine
Cataract
Same age mouse
looks much younger
Hair loss
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845101/
Normal Age Same Age / Senolytic Treated
Internal measures show improved organ function in senolytic-treated group
This finding may indicate that humans scheduled to die at age 80 may
live to age 100 in relatively good health…using this one intervention

Mayo Clinic study demonstrates improved organ
function when Senescent Cells are removed
https://www.cnbc.com/2018/08/29/-jeff-bezos-is-backing-this-scientist-who-is-working-on-a-cure-for-aging.html
Bent spine
Cataract
Same age mouse
looks much younger
Hair loss
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845101/
Normal Age Same Age / Senolytic Treated
 Improved kidney function.
 Hearts more resilient to stress.
 Extended lifespans.

Scientific Discovery and the Future of Medicine
Journal of the American Medical Association
“Interventions aimed at eliminating those senescent cells,
commonly called senolytic, have also been shown to improve health
and extend life in various mouse disease models.
“If senolytics are shown to be safe and effective in humans, they could
transform care of older adults and patients with multiple chronic diseases.”
JAMA. Published online September 17, 2018. doi:10.1001/jama.2018.12440
Aging, Cell Senescence, and Chronic
Disease: Emerging Therapeutic Strategies
“…many human pathologic conditions are associated with the presence of senescent cells.”

This drug cocktail reduced signs of age-related
diseases and extended life in mice and human cells
Senolytic Delay May = Death
“Group led by Mayo Clinic anti-aging researcher James Kirkland not only offers a clear look at
the power of senescent cells to drive the aging process, but also a pharmaceutical cocktail that,
in mice at least, can slow and even reverse it.
Compared to mice who aged normally, those who started getting the dasatinib-quercetin cocktail at
an age equivalent to 75 to 90 yearsin humans ended up living roughly 36% longer, and with better
physical function.
In human cells in a test tube and in mice bearing human senescent cells, the dasatinib-quercetin
cocktail showed equally promising results, targeting senescent cells while leaving other cells intact.
Aging…is beginning to look more and more like a disease — and a treatable one at that.
ScientistsAre Testing
CancerDrugstoSlowDownAging July 10, 2019

Journal of the American Medical Association
“Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies.” JAMA Online-Sept 17 2018
“…patients should be advised not to self-medicate with
senolytic agents or other drugs that target fundamental
aging processes in the expectation that conditions alleviated
in mice will be alleviated in people. Senolytics represent a
new potential treatment approach, and the adverse effects
of these therapies remain to be elucidated.”
Experts Tell Us to Wait…
Scientific Discovery and the Future of Medicine

First Published Human
Senolytic Clinical Trial
Jan 7, 2019
THE LANCET

Dr. James Kirkland - Mayo Clinic
https://newsnetwork.mayoclinic.org/discussion/removal-of-
zombie-cells-alleviates-causes-of-diabetes-in-obese-mice/
Jan. 8, 2019
“This is like a glimmer
that it might actually
work. The results were
impressive.
All 14 (humans) got
better in their
functional ability.”
https://www.telegraph.co.uk/science/2019/01/08/drug-
clear-zombie-cells-body-could-first-anti-ageing-treatment/

Drug to clear 'zombie cells' from body could be first
anti-aging treatment after ‘impressive’ human trial
https://www.telegraph.co.uk/science/2019/01/08/drug-clear-zombie-cells-body-could-first-anti-ageing-treatment/
Jan. 8, 2019
“A drug to fight aging may finally
be on the horizon after the
first trial in humans showed
‘impressive’ results.”
“The treatment clears out dead
cells even when the immune
system no longer can.”

The treatment protocol consisted of dasatinib and quercetin
https://www.telegraph.co.uk/science/2019/01/08/drug-clear-zombie-cells-body-could-first-anti-ageing-treatment/
Jan. 8, 2019
“Previously animal studies have
shown that removing these cells
reverses the aging process,
extends lifespan, and restores
lost youth”
“Now for the first time scientists in
the US have shown improvements
in humans using a drug that
sweeps away the defunct cells.”

 Reduced glucose levels
 Improved insulin sensitivity
 Decline in inflammatory factors
 Return to normal fat cell function
 Improved kidney & heart function
Removal of 'zombie cells' alleviates
causes of diabetes in obese mice Mar 25, 2019
Removal of senescent cells:
https://www.sciencedaily.com/releases/2019/03/190325120339.htm

“National Institute on Aging
Intramural Research Program
added substantial proof that
senolytics, the golden child of
anti-aging drugs, rescue memory
loss in Alzheimer’s disease, at
least in mice genetically
engineered to accumulate
amyloid clumps in their brains.”
“Senolytic therapy alleviates Aβ-associated
oligodendrocyte progenitor cell senescence and
cognitive deficits in an Alzheimer’s disease model”
Apr. 1, 2019
Senolytics Effective in
Mouse Model of Alzheimer’s
https://www.nature.com/articles/s41593-019-0372-9

“The treated mice also had fewer
senescent cells in their hippocampus,
the brain’s main memory center, and
navigated complex water mazes better
than their peers.”
Apr. 15, 2019
Dasatinib + Quercetin Mitigates Alzheimer’s
and Improves Cognitive Performance
https://singularityhub.com/2019/04/15/senolytics-show-promise-against-alzheimers-in-mice/
“The team squirted the drug cocktail
(dasatinib and quercetin) into their
Alzheimer’s mice once a week for 11 weeks.”
“Positive results came fast: the
mice’s beta-amyloid levels dropped
within three months.”

Apr. 15, 2019
Senolytics Restore Memory
“Our findings pave the way for
future preclinical and clinical
studies that will test the
hypothesis that senolytic
therapies can … preserve brain
function in [Alzheimer’s] and
other age-related
neurodegenerative disorders…”
https://singularityhub.com/2019/04/15/senolytics-show-promise-against-alzheimers-in-mice/
“In a series of memory tests, the treated mice regained
their ability to learn and memorize complex mazes.”
Conclusions from the study

“Aged‐senescent cells contribute to impaired heart regeneration.” Aging Cell; June 2019
Senescent Cells Thwart Progenitor Cell Regeneration
When senolytics ( )
were administered in vivo to elderly
mice, cardiac progenitor cells reactivated
and began remodeling the aged hearts.
Senescent progenitor cardiac cells
are unable to replicate, differentiate,
regenerate or restore cardiac
function following transplantation
into infarcted mouse heart.

“Aged‐senescent cells contribute to impaired heart regeneration.” Aging Cell; June 2019
Senescent Cells Thwart Progenitor Cell Regeneration
“The present findings
provide new insights
into therapies that
target senescent cells
to prevent an age-
related loss of
regenerative capacity.”

“Senescent cells – also known as
zombie cells – form in the heart during
aging and lead to heart failure.”
“Newcastle scientists, in collaboration
with researchers in the Mayo Clinic…
not only discovered how this process
takes place in the heart but also how
it can be reversed or treated.”
Newcastle University scientists
are killing zombie cells to reverse
age-related damage in the heart
Feb.8,2019
British Heart
Foundation
https://www.bhf.org.uk/what-we-do/news-from-the-bhf/news-archive/2019/february/newcastle-university-scientists-are-killing-zombie-cells-to-reverse-age-related-damage-in-the-heart

“Senescent cells – also known
as zombie cells – form in the
heart during aging and lead to
heart failure.”
“Newcastle scientists, in
collaboration with researchers in
the Mayo Clinic… not only
discovered how this process takes
place in the heart but also how it
can be reversed or treated.”
Newcastle University scientists
are killing zombie cells to reverse
age-related damage in the heart
Feb.8,2019
British Heart
Foundation
https://www.bhf.org.uk/what-we-do/news-from-the-bhf/news-archive/2019/february/newcastle-university-scientists-are-killing-zombie-cells-to-reverse-age-related-damage-in-the-heart

“Scientists believe it may be possible to
reverse the heart damage caused by aging”
Rhys Anderson et al. Length‐independent telomere damage drives post‐mitotic
cardiomyocyte senescence, The EMBO Journal (2019). DOI: 10.15252/embj.2018100492
Feb. 11, 2019
"We saw that removing senescent cardiomyocytes from the hearts of
aged mice, both genetically and using drugs, was able to restore
cardiac health – essentially removing the damage caused by aging.
This data provides critical support for the potential of using
medicines to kill zombie cells. If this is validated through clinical
trials it would provide us with a new way of treating cardiac diseases."

New Avenues for Improved Cardiac Regeneration Therapy
Length‐independent telomere damage
occurs in aging post‐mitotic cardiomyocytes.
Mitochondrial dysfunction and reactive
oxygen species drive telomere dysfunction
in aged cardiomyocytes.
Senescent cell clearance reduces
hypertrophy and fibrosis in aged hearts.
Findings on potential cardiac
regeneration using senolytics:
DOI 10.15252/embj.2018100492
Published online 08.02.2019 The EMBO Journal (2019)

Dr. Alan Green at his practice in Little Neck, NY
now has 500+ patients using rapamycin with
100+ patient adding dasatinib, fisetin and
quercetin .
Dr. Green’s Anti-Aging Cocktail
1) Rapamycin
2) Dasatinib
3) Fisetin
4) Quercetin
Clinical Use in U.S.
https://senolyticstreatment.com/

2022 Experimental Dasatinib Dose Schedule
Afterreviewingcontraindicationswithyourdoctor,considerthefollowing ONCEmonthly:
Repeat each month. Do not take rapamycin week you take senolytic.
Rapamycin may impede senolysis. Register for updates at: age-reversal.net
Day One: Dasatinib 100 mg
Theaflavins 275 mg
Quercetin 25 mg (bioavailable)
Fisetin 56 mg (bioavailable)
Day Two: Repeat Day One doses unless
dasatinib side effects manifest.

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
Exosomes

› Older partners paired with young
rats lived for four-to-five months
longer than controls.
› This life span extension is the
equivalent of 10-12 human years.
› Source: New York Academy of Sciences, (1972 Nov) Vol. 34, No. 7, pp. 582-7.
› in 1972 researchers at the University of California
studied the life spans of old–young circulatory
connected rat pairs.

https://www.newscientist.com/article/2311876-we-may-now-know-why-young-blood-can-have-rejuvenating-effects/
Packages of RNA and proteins that bud off
from cells have reversed some signs of
aging in mice, and they may account for
the rejuvenating effects of young blood.
March10,2022
“…itreversedseveralsignsofaging,
includingboostingmusclestrength
andhairgrowthandimproving
coordinationandendurance.”
AsFeatured inNewScientist

https://doi.org/10.1016/j.stem.2022.04.017
June 2nd, 2022
Research Highlights:
Youthful hematopoietic stem cell
function restored.
“Rejuvenatingfactors”identified in youngblood.
Immune senescence of lymphocytes mitigated.
Heterochronic Parabiosis Induces Stem Cell Revitalization
and Systemic Rejuvenation Across Aged Tissues

Stanford University scientists
previously showed that transfused
serum from 12-to-15-month age
mice into old mice reverses some
signs of brain aging.
Kathlyn J. Gan et al. Specific factors in blood from young but not old mice directly promote synapse
formation and NMDA-receptor recruitment, Proceedings of the National Academy of Sciences (2019).
DOI: 10.1073/pnas.1902672116
JUNE 3, 2019

Researchers find synapse-boosting factors in young blood
Available at: https://medicalxpress.com/news/2019-06-synapse-boosting-factors-young-blood.html. Accessed June 4, 2019.
June 4, 2019
Stanford University researchers used serum from
15-day old (very young) mice and discovered:
“ ”

https://medicalxpress.com/news/2018-12-scientists-youth-factor-blood-cells.html
“Scientists identify 'youth factor' in
blood cells that speeds fracture repair”
Medical press Dec. 5, 2018
More than 800,000 Americans a year are hospitalized
because of fall injuries, including broken hips.
Mortality rates are high, especially in elderly men.
Duke Health researchers showed
introducing bone marrow stem cells to
a bone injury can expedite healing.
New study by same Duke-led team has
pinpointed "youth factor" inside bone
marrow stem cells that can have a
rejuvenating effect on tissue.

Huang, Qi, Yichun Ning, Dong Liu, Ying Zhang, Diangeng Li, Yinping Zhang, Zhong Yin et al. “A young blood
environment decreases aging of senile mice kidneys." The Journals of Gerontology: Series A 73, no. 4 (2017): 421 -428.
A Young Blood Environment Decreases Aging of Senile Mice Kidneys
After parabiosis, kidney tubule and interstitial tissue scores
in the old group were significantly lower (improved) than in
the old control group given only young blood.

April 21st, 2020
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.
Young plasma treatment more
than halved the epigenetic ages
of blood, heart and liver tissues.
Epigenetic clock measures
indicate systemic rejuvenation.

https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1.full
April 21st, 2020
Cellular senescence
reduced in vital organs.
Young Plasma fraction
improvesorganfunctionand
measures of cognition.
The effect of plasma
fraction treatment on
cellular senescence:
After a 155-day
treatment period, the
brains of young plasma
treated old rats and
young rats were stained
for senescence-
associated “beta-
galactosidase”, whose
activity on the substrate
turns senescent cells
blue in color.

Within 10 days of
young plasma fraction
treatment the physical
capacities of old rats are
indistinguishable from
that of the young rats.
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.
Grip Strength Analysis
April 21, 2020

July 10th, 2020
Blood Factors Transfer Beneficial Effects of Exercise
on Neurogenesis and Cognition to the Aged Brain
Researchers transfused plasma from old mice
who were allowed to exercise for 6 weeks to
other old mice who were not allowed.
Rodents who received the plasma from the
active mice grew roughly twice as many new
neurons in the hippocampus as controls.
https://www.sciencemag.org/news/2020/07/protein-blood-exercising-mice-rejuvenates-brains-couch-potato-mice
Couch potato mice receiving this blood eight
times over 3 weeks did nearly as well onlearning
and memory tests as the exercising mice.

“...aged mice that received plasma from
middle-age or old mice that exercised
showed beneficial effects in their brains
without hitting the treadmill.”
https://science.sciencemag.org/content/369/6500/167
An enzyme generated in livers
of exercising mice demonstrate
similar brain restoring effects.
Blood factors transfer beneficial
effects of exercise to the aged brain

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
Hyperbaric

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

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
NAD+

Life Sustaining Benefits of NAD+

NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice.
Science 17 Jun 2016: Vol. 352, Issue 6292, pp. 1436-1443 DOI: 10.1126/science.aaf2693
NAD+ Protects Stem Cells in Aging Mice

How to Boost Cellular NAD+
►Persons under 50 years supplement
with 250-500 mg/day of nicotinamide
riboside.
►Older individuals need NAD+ infusions
or patches.
►Follow up NAD+ therapy with 250-
500mg/day of nicotinamide riboside.

Feb. 28, 2018
Magazine
Is an Anti-Aging Pill on the
Horizon?
“NAD+ is the closest we’ve gotten
to a fountain of youth,” says David
Sinclair (Harvard Medical School).
“It’s one of the most
important molecules for life
to exist, and without it,
you’re dead in 30 seconds.”
http://amp.timeinc.net/time/5159879/is-an-anti-aging-pill-on-the-horizon?

March 22, 2018
“We’ve discovered a way to reverse vascular
aging by boosting the presence of naturally
occurring molecules in the body that augment
the physiological response to exercise.”
The active molecules:
SIRT1 and NAD+
David Sinclair, Ph.D. professor in
the Department of Genetics at
Harvard Medical School
Impairment of an Endothelial NAD -H 2 S Signaling Network
Is a Reversible Cause of Vascular Aging. Cell, 2018; 173 (1):
74 DOI: 10.1016/j.cell.2018.02.008`

May 21, 2018
NAD+ May Improve Heart Function
”Stabilizing the intracellular NAD+ level represents a promising
therapeutic strategy to improve myocardial bioenergetics and
cardiac function.“
“In this issue of Circulation, Diguet et al5 report exciting data
suggesting that supplementation with a NAD+ precursor,
nicotinamide riboside, reduces cardiac dysfunction in preclinical
models of heart failure.”
http://circ.ahajournals.org/content/137/21/2274
(NAD+ patches or infusions needed for humans to obtain equivalent dose)

NAD+ Restoration Turns Real in 2014
 Since 2001, Life Extension™
has been seeking ways to
restore NAD+.
 NAD+ is a compound found in
young cells that turns “off”
degenerative processes.
 Affordable methods of
boosting NAD+ are available.

July 9, 2018
NAD+ Restores Cellular DNA Repair
►NAD+ depletion turns off
DNA repair enzymes.
►Increase NAD+ with
nicotinamide riboside.
Boost NAD+ Blood Levels

“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.”

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

Impact of Severe NAD+ Deficit
 Tremors
 Depression
 Arterial stiffness
 Circadian rhythm imbalance
 Pro-youth genes turned off
 Restless leg syndrome
 Cellular senescence
 Sarcopenia
 Death

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
SGLT2 Inhibitors

SGLT2 Inhibitors
Potential Anti-Aging Strategy
SGLT2 = Sodium-Glucose Cotransporter2
These drugs inhibit SGLT2 in kidneys to
flush away excess glucose:

Sodium-Glucose in
Sodium-Glucose out
Normal
or
SGLT2 Inhibitor
More Sodium-Glucose
removed in Urine
Kidneys return about 100% of Glucose to Circulation
SGLT2 inhibitors redirects Sodium-Glucose to Urine

Prescription Drug Lets You Urinate
Away Excess Salt and Sugar
Sodium-Glucose Cotransporter-2 (SGLT2)
inhibitors approved to treat type II diabetes.
SGLT2 inhibitors block a kidney
receptor that recovers glucose and
sodium from filtered blood. Enables
some sodium-glucose to urinate out.

PERSISTENTLY ELEVATED GLUCOSE
Glycation of
Proteins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951818/
High Blood Glucose Contributes to Glycation

https://news.cornell.edu/stories/2021/03/excess-blood-sugar-promotes-clogging-arteries-study
“Excess sugar in the blood, the
central feature of diabetes, can
react with immune proteins to
cause myriad changes in the
immune system, including
inflammatory changes that
promote atherosclerosis.”
March 23rd, 2021

Some of the Many Dangers of High Glucose:
 Atherosclerosiswhichcausesreducedbloodflow,arterial
blockages and contributes to high blood pressure.1
 Endothelial dysfunction which can damage every organ.
Most visibly eyes, kidneys, heart, brain & peripheral nerves.4,5
 Oxidative stress and inflammation
which increases risk of cancer.2,3
 Reduced insulin sensitivity and metabolic dysfunction
which cause increased body fat and high cholesterol.6
https://pubmed.ncbi.nlm.nih.gov/32155866/ https://pubmed.ncbi.nlm.nih.gov/31757028/
https://pubmed.ncbi.nlm.nih.gov/31242027/ https://pubmed.ncbi.nlm.nih.gov/25126408/ https://pubmed.ncbi.nlm.nih.gov/26566492/
2.
1.
4. 5. 6.
https://pubmed.ncbi.nlm.nih.gov/28098811/
3.

SGLT2 Inhibitors reduce
GLUCOSE
and more to delay aging!

https://onlinelibrary.wiley.com/doi/10.1002/0471266949.bmc277
SGLT2 inhibitors show potentialto
protectagainstdiabetic nephropathy:
1) Improved glycemic control and
lower blood pressure.
2) Reducedglomerular hyperfiltration
3) Decreased inflammation-fibrosis of
proximal tubular cells in response to
hyperglycemia, and albuminuria.
SGLT2 Inhibitors Benefit the Kidneys

Aug. 17, 2017
Ten Thousand Patient NEJM Study Finds
Multiple Major Benefits of SGLT-2 Inhibitors
https://www.nejm.org/doi/10.1056/NEJMoa1611925
ThosetakingaSGLT2inhibitorwere27%lesslikelytoprogress
toalbuminuria(proteininurine)comparedtoplacebo.
Regression of albuminuria occurred 70% more frequently
in the SGLT2 inhibitor group, indicating an improvement
in advanced stage chronic kidney failure patients.
Among type II diabetic patients taking a SGLT2 inhibitor,
there were 40% fewer instances of a massive drop in
eGFR, a need for kidney dialysis or transplant, or death
from kidney causes compared to the placebo arm.

Pathophysiologyofdiabetickidneydisease:impactofSGLT2inhibitors
https://www.nature.com/articles/s41581-021-00393-8
Known Kidney Benefits as of 2021:

https://link.springer.com/article/10.1007/s00125-021-05424-4
SGLT2 inhibitor associatedwith50% reducedincidenceofKidney Stones

https://www.nature.com/articles/s41591-021-01536-x
SGLT2 inhibitors Benefit the Heart
⬇ Microvascular Dysfunction
⬇ Inflammation & Oxidative Stress
⬆ Myocardial Energy Production
⬆ Systemic Endothelial Function
⬆ Fatty Acid Oxidation (heart muscle)
⬆ Insulin Sensitivity (heart muscle)

Managing Cardiovascular & Kidney Disease
https://www.nejm.org/doi/full/10.1056/NEJMra2115011
May 26th, 2022
“SGLT2 inhibitors are responsible for major paradigm
shifts in the care of patients with or at high risk for heart
failure, progression of chronic kidney disease, or both.
Theseagentsalsoreducetheriskofend-stagekidneydisease
inpatientswithtype2diabetesandchronic kidneydisease.”
SGLT2 inhibition improves cardiovascular outcomes
in patients with heart failure …regardless of whether
the patients have type 2 diabetes…

https://pubmed.ncbi.nlm.nih.gov/27009625/
Meta-analysis of 57 Clinical Trials Finds:
Clinical Cardiovascular Benefits of SGLT2 Inhibitors
37%reduceddeathfromcardiovasculardisease
56% reduced all-cause mortality and 49% reduced
risk of cardiovascular disease compared to insulin
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485030/
39%reducedriskofheartfailurehospitalization
37k Patient Swedish Study Finds:
309k Patient Study Finds:
https://pubmed.ncbi.nlm.nih.gov/28522450/

1. https://pubmed.ncbi.nlm.nih.gov/32854852/
SGLT2 inhibitors Benefit the Brain
“Our findings revealed a previously unobserved
association between ≥3 years SGLT2 inhibitor use
and improved cognitive scores globally and in
language domain and executive function.”
2. https://content.iospress.com/articles/journal-of-alzheimers-disease/jad215678
Type 2 diabetes increases Alzheimer’s risk.
SGLT2 inhibitors being studied to prevent or
reduce progress of Alzheimer's pathology.1
Results from separate clinical study:2

The Clinical Effects of SGLT2
Inhibitors on Cancer Development
https://pubmed.ncbi.nlm.nih.gov/33562380/
SGLT2 Inhibitors are fairly novel drugs, being first
approved by the FDA for use in 2013, long term clinical
studies still don’t exist and early studies found little
correlation between its use and overall cancer risk.
https://pubmed.ncbi.nlm.nih.gov/34929299/
2022 meta-analysis of 20 Clinical Trials Finds:
SGLT2 inhibitors linked to 65% reduction
in cancer risk in hyperglycemic patients.
Note:

https://pubmed.ncbi.nlm.nih.gov/28763435/ |https://pubmed.ncbi.nlm.nih.gov/29205334/
SGLT2 inhibitor-therapy induces AMPK-mediated cell cycle
arrest and apoptosis in breast and thyroid cancer cells.
SGLT2 Inhibitors Slow Cancer Growth
https://pubmed.ncbi.nlm.nih.gov/33068934/ |https://pubmed.ncbi.nlm.nih.gov/35148777/
Canagliflozin(SGLT2inhibitor)blocksComplex-Iincellularrespiration,
limiting cellular proliferation of prostate & lung cancer cells.
https://pubmed.ncbi.nlm.nih.gov/27689018/
Dapagliflozin (SGLT2 inhibitor) regulates the cell cycle, apoptosis &
reduces glucose uptake in renal cell carcinoma and canagliflozin
doesthesameinhepatocellularcarcinomaandwasshowntoreduce
tumor growth & angiogenesis in a tumor graft model in mice.
SGLT2inhibitorsslow cancer by reducingglucosesystemically
& directly- many cancers expressSGLT2tohelp uptakeglucose

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
Gene Therapy

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

Remarkable life extension in mice!
May 10th, 2022

May 10th, 2022
Reference: Jaijyan et al. New intranasal and injectable gene therapy for healthy life extension. Proc Natl Acad Sci U S A.
2022 May 17;119(20):e2121499119. doi: 10.1073/pnas.2121499119. PMID 35537048.
• Researchers tested two gene therapies in mice
• Telomerase (TERT) and follistatin
• Eight mice in each treatment group
• Gene therapy given monthly
• Started at 18 months (about age 56 in humans)
• CMV was used to deliver gene therapies

May 10th, 2022
Reference: Jaijyan et al. New intranasal and injectable gene therapy for healthy life extension. Proc Natl Acad Sci U S A.
2022 May 17;119(20):e2121499119. doi: 10.1073/pnas.2121499119. PMID 35537048.
TERT (telomerase reverse transcriptase) Gene Therapy:
• All control mice dead at age 30 months
• All TERT-treated mice alive at 30 months
• 50% (4 of 8) TERT-treated mice alive at 38 months
• 12.5% of mice (1 of 8) of TERT-treated mice alive at 40 months

May 10th, 2022
Reference: Jaijyan et al. New intranasal and injectable gene therapy for healthy life extension. Proc Natl Acad Sci U S A.
2022 May 17;119(20):e2121499119. doi: 10.1073/pnas.2121499119. PMID 35537048.
Follistatin gene therapy:
• Follistatin was also found to extend lifespan
• All control mice were dead at age 30 months
• 56.25% (9 of 16) follistatin-treated mice alive at 34 months
• The last follistatin-treated mice died between 36 and 38 months

May 10th, 2022
Reference: Jaijyan et al. New intranasal and injectable gene therapy for healthy life extension. Proc Natl Acad Sci U S A.
2022 May 17;119(20):e2121499119. doi: 10.1073/pnas.2121499119. PMID 35537048.
• Telomerase (TERT) gene therapy associated with 41.4% extension of
median lifespan
• Follistatin gene therapy was associated with 32.5% extension of median
lifespan
• Researchers report benefits seem to wane if treatment was stopped
• CMV appeared to have no effect on lifespan in this model

May 10th, 2022
Reference: Jaijyan et al. New intranasal and injectable gene therapy for healthy life extension. Proc Natl Acad Sci U S A.
2022 May 17;119(20):e2121499119. doi: 10.1073/pnas.2121499119. PMID 35537048.
All control mice
dead at 30 months
50% of TERT-treated mice
still alive at 38 months

May 10th, 2022
Reference: Jaijyan et al. New intranasal and injectable gene therapy for healthy life extension. Proc Natl Acad Sci U S A.
2022 May 17;119(20):e2121499119. doi: 10.1073/pnas.2121499119. PMID 35537048.
Human Life Span Median Equivalent up 110 Years

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

Perpetual Project Goals
Age-Reversal.Net
Utilize blood & other tests to evaluate safety & potential efficacy.
Robust communications amongst the group members, share test
result data & suggestions on potential ways to improve outcomes.
Accelerate & validate potential rejuvenation technologies to
benefit all of humanity…including Perpetual Project members.
Rapidly convey data to members and the public so that
medical professionals, scientists, and the lay persons are
aware of scientific findings that may save human lives.

Join the Perpetual Project private
association and receive updates
about regenerative medicine initiatives
www.age-reversal.net
How to Enroll

Regenerative Medicine Options
Island House Hotel, The Bahamas
William Faloon
April 20th 2023
The Perpetual Project