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www.healincsummit.com
Atlantis Hotel – The Bahamas
April 29th, 2024
Age Reversal Advances from Cells
to Mice, Monkeys and Humans
Bill Faloon
Life Extension®
Decades
Track Record Available at: https://www.lifeextension.com/about/life-extension-story/history
1981
1985
1986
1992
1983
June 12, 2018
has pursued
immortality for
decades.
Now he's got lots of
company. What does
https://www.popsci.com/forever-man-immortality-science/
June12,2018
https://www.technologyreview.com/magazine/2019/09 September
2019
“Later this year, at a conference
of longevity enthusiasts called
RAADfest, to be held in Las
Vegas, Bill Faloon plans to take
the strategy one step further
with what he has been calling
the “Perpetual Clinical Trial.”
“OLD AGE IS OVER!”
February 28, 2021
https://www.aging-us.com/article/202712/text
“When cells were reprogrammed with a 6-factor
cocktail the (degenerative) alterations were
fully reversed and cells fully rejuvenated.”
This 2021 published review summarized
age-reversal impact of cell reprogramming.
Funded by Bill Faloon’s group + other
charitable donors.
April 8th, 2023
“First anti-aging pills to hit shelves in 2028, expert
predicts – as Silicon Valley races to conquer death”
ChatGPT boss Sam Altman has invested
$180 million in anti-aging biotech firm.
Long line of Silicon Valley billionaires throw
considerable wealth behind the science.
Jeff Bezos put $3 billion into anti-aging startup.
Pills to help people reverse the effects of aging
“could be on the market in the next 5 years”
https://www.dailymail.co.uk/sciencetech/article-11844303
SamAltman
“Mr. Kurzweil believes we may achieve immortality
as soon as 2030, thanks to the development of
‘nanobots,’ tiny robots that will constantly repair
our bodies at the cellular level. He predicts people
will soon be able to eat whatever they want and
stay trim while nanobots in their bodies cure
diseases, create immunities and heal injuries.”
| May 2nd, 2023
www.wsj.com/articles/immortality-isnt-all-its-cracked-up-to-be-nanobots-science-health-death-penalty-healthcare-33ae5abf
“Even if this fantastical breakthrough becomes
reality, is human immortality a good thing?”
“ ”
“ ”
- May 19th, 2023
technologyreview.com/2023/05/19/1073374/i-just-met-the-founders-of-a-would-be-longevity-state/
“I just met the founders of a would-belongevity state”
“What if I told you there’s a group of people
who think death is morally bad…Who seek to
create a new state with its own laws that
expedite the development of longevity drugs,
partly by encouraging biohacking and self-
experimentation?”
| July 10th, 2023
https://www.wsj.com/articles/longevity-clinics-aging-living-longer-2b98e773
“The Longevity Clinic Will See You Now…”
“The clinics cater to a growing number of people obsessed with fighting aging”
“ThecenterscapitalizeonAmericans’ obsessionwith
livinglongeranddesireforpersonalizedmedicalcare.”
“They are often wealthy people in their
40s to 60s who are seeing signs of aging.”
“Venture-capital investment in longevity clinics
more than doubled between 2021 and 2022,
from $27 million to $57 million globally.”
Singapore Opens World’s First Healthy
Longevity Clinic in a Hospital
August 31, 2023
The Healthy Longevity Clinic at Alexandra Hospital is
partnering with National University of Singapore to:
Optimize health and reduce burden of age-related disease
Test evidence-based treatments including repurposed drugs
Conduct clinical research on new longevity technologies
https://www.lifespan.io/news/singapore-opens-worlds-first-healthy-longevity-clinic
Healthy Longevity Clinic – Singapore to
rigorously test clinical efficacy-/safety of:
Per an Email to William Faloon from Healthy Longevity Clinic - Nov. 6, 2023
“The human research model combines evidence-based interventions with personalized
medicine, remote monitoring, and health coaching. Evaluation criteria include clinical
outcomes, cost-effectiveness, implementation research, and stakeholder satisfaction.”
1. Rapamycin - Early 2024
2. Taurine - Mid 2024
3. Glycine - Mid 2024
4. NMN - Mid 2024
August 2nd, 2023
“There's one major key to unlocking extreme longevity.”
“If humans living for 1,000
years seems like a complete
stretch, aging expert João
Pedro de Magalhães will do you
one better: how about humans
living for 20,000 years?”
https://www.popularmechanics.com/science/health/a44713943/humans-can-live-20000-years-aging-expert/
“An Aging Expert Thinks Humans Can
Live for 20,000 Years. He's Not Crazy.”
Aging is Now Optional w/ David Sinclair | EP#60 | youtube.com/watch?v=Jk_GcwkfJGs
Peter Diamandis Interviews David Sinclair
David Sinclair, heads the Sinclair Lab, a
Harvard lab working on a cure for aging.
“I know there isn’t, it’s not
even a question really.”
When asked, is there is an
upper limit to human aging?
He responds:
Aug 24, 2023
| September 1st, 2023
Saudi’s allocated> $1 billion a yearto developtreatmentsforaging.
“Saudi Arabia Is Dangling Billions for Research
on Aging. Scientists Are Lining Up to Take It.”
Since the Saudi foundation’s start in July 2022, it
has dispersed less than $20 million. They expect
to ramp up to $1 billion as projects are selected.
American Federation for Aging Research got $7.76 million.
U of Pittsburgh got $375k for a senescence study.
Norn Group, U.S. nonprofit received $7 million.
Grants thus far:
Sept. 11, 2023
The Economist Dedicates an
Entire Issue to Age Reversal
https://www.economist.com/technology-quarterly/2023-09-30
https://www.economist.com/technology-quarterly/2023/09/25/slowing-human-ageing-is-now-the-subject-of-serious-research
https://www.economist.com/technology-quarterly/2023/09/25/some-claim-human-lifespans-can-be-lengthened-indefinitely
https://www.economist.com/technology-quarterly/2023/09/25/what-the-young-can-give-to-the-old
https://www.economist.com/technology-quarterly/2023/09/25/ageing-bodies-need-to-get-rid-of-decrepit-cells
https://www.economist.com/technology-quarterly/2023/09/25/fighting-ageing-requires-properly-equipped-cells
https://www.economist.com/technology-quarterly/2023/09/25/eating-fewer-calories-can-ward-off-ageing
This dosing regimen is practical for humans & a primate study is
being designed using same exosome-rich young plasma fraction.
“Cuts old age in half”
https://link.springer.com/article/10.1007/s11357-023-00980-6/
February 2024
Intriguing dosing schedule:
Exosome-rich young plasma fraction
infused IV (tail) every other day for 8 days.
95 days later repeat once
Exosome-Rich Young Plasma Fraction Treatment Protocol
Plasma Fraction Reverses Epigenetic Age
Liver: 74.6% Blood: 64.3%
Heart: 46.5% Brain: 24.4%
(hypothalamus)
February, 2024
Refined
Exosome
Concentrate
Horvath, S., Singh, K., Raj, K. et al. Reversal of biological age in
multiple rat organs by young porcine plasma fraction. GeroScience 46,
367–394 (2024). https://doi.org/10.1007/s11357-023-00980-6
Average DNAm age reduced as much as 67.4%
Two-year-old rats (circa 60-year-old humanage)
treated with “exosome fraction of plasma” from
young adult pigs reduced epigenetic age by:
https://link.springer.com/article/10.1007/s11357-023-00980-6/figures/2
February 2024
Robust Age Reduction measured by DNAmAge in Tissues
https://link.springer.com/article/10.1007/s11357-023-00980-6/figures/2
February 2024
Robust Age Reduction measured by DNAmAge Human-Rat Tissue
Beneficial Reductions in Epigenetic Age
https://link.springer.com/article/10.1007/s11357-023-00980-6
February 2024
In young plasma-treated old rats, epigenetic ages
of blood, liver, and heartreduced to levels…
“comparable with young rats.”
LiverFunctionMarkersRestoredtoYouthfulRanges
https://link.springer.com/article/10.1007/s11357-023-00980-6/figures/3
February 2024
Reversal ofConventionalMeasuresof Risks
https://link.springer.com/article/10.1007/s11357-023-00980-6/figures/3
February 2024
Restoration of Youthful Kidney Function Markers
https://link.springer.com/article/10.1007/s11357-023-00980-6/figures/3
February 2024
 Note creatinine levels returned to young, healthy ranges 150 days posttreatment.
 This indicates potential of reversing chronic kidney disease.
Young Plasma Research Projects
Volumesofpublishedstudiesdescriberejuvenationeffectsofyoungplasma.*
Several protocols under study, including periodic healthy young
plasma infusions or removing senile blood proteins via apheresis with
albumin/immunoglobulin or healthy young plasma replacement.
*References on the following slides
Projects in planning to assess effects of healthy young plasma
regenerative potential in kidney, heart, liver, & brains of old humans.
Young human plasma already found to regenerate brains of old rats.
Published Reports Describing
Regenerative Potential of Young Plasma
Preclinical Assessment of Young Blood Plasma for Alzheimer Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172595/
The Plasma for Alzheimer Symptom Amelioration (PLASMA) Study (PLASMA)
https://clinicaltrials.gov/study/NCT02256306
A randomized, controlled clinical trial of plasma exchange with albumin
replacement for Alzheimer's disease: Primary results of the AMBAR Study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984263/
The Stanford Parkinson's Disease Plasma Study (SPDP)
https://clinicaltrials.gov/study/NCT02968433
Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma
for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439869/
Preclinical Assessment of Young Blood Plasma for Alzheimer Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172595/
Young Blood Plasma Administration to Fight Alzheimer's Disease?
https://www.liebertpub.com/doi/10.1089/rej.2017.1940
Platelet factors attenuate inflammation and rescue cognition in ageing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468395/
Young blood plasma reduces Alzheimer's disease-like brain pathologies and
ameliorates cognitive impairment in 3×Tg-AD mice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278124/
Plasma-Based Strategies for Therapeutic Modulation of Brain Aging
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694331/
Young Plasma Studies Continued…
Young Plasma Studies Continued…
Aging and age-related diseases with a focus on therapeutic potentials of young blood/plasma
https://link.springer.com/article/10.1007/s00210-023-02657-5
Circulating plasma factors involved in rejuvenation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746393/
Plasma from Young Rats Injected into Old Rats Induce Antiaging Effects
https://www.liebertpub.com/doi/10.1089/rej.2020.2354
The effect of aging on the bone healing properties of blood plasma
https://www.injuryjournal.com/article/S0020-1383(21)00426-5/fulltext
Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522807/
Undulating changes in human plasma proteome profiles across the lifespan
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062043/
Young Plasma Rejuvenates Blood Dna Methylation Profile, Extends Mean Lifespan And
Improves Physical Appearance In Old Rats
https://pubmed.ncbi.nlm.nih.gov/38430547/
This dosing regimen is practical for humans & a primate study is
being designed using same exosome-rich young plasma fraction.
“Cuts old age in half”
https://link.springer.com/article/10.1007/s11357-023-00980-6/
February 2024
Intriguing dosing schedule:
Exosome-rich young plasma fraction
infused IV (tail) every other day for 8 days.
95 days later repeat once
Exosome-Rich Young Plasma Fraction Treatment Protocol
https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glae071/7618060
March 2, 2024
March 2, 2024
Young Plasma Increases Median Lifespan
Beginning at age 25.6 months,one rat group given
young plasma every other week until death.
Beginning human equivalent of 60-65 years
March 2, 2024
Survival curve of no treatment group
began to decline at 26 months.
From age 26 to 30 months,
none of the young plasma
animals died.
The same age control group received no treatment.
https://pubmed.ncbi.nlm.nih.gov/
38430547/
Significant 9.1% improvement in median lifespan of the young plasma
treated group (red) compared with no treated controls (black).
DNA methylation testing measures epigenetic age and is considered
the most accurate method of assessing future morbidity/mortality risk.
Young Plasma Reverses Epigenetic Age
Improved insulin sensitivity, better immune
& metabolic health, reduced inflammation!
Epigenetic age stayed consistently lower in young
plasma group until natural death with indications of:
DNA methylation age of young plasma-treated
rats beneficially fell below the control group
The longest-lived animal in control (no treatment) group.
That’s where gene therapy
can come to the rescue!
Indicates young plasma can
delay median death age but
may not confer super longevity
One interesting caveat…
Reprogram old cells into
induced pluripotent stem
cells or young adult cells
that can theoretically
regenerate tissues forever.
Yamanaka Transcription Factors –
There are about 1500 gene regulatory transcription factors
Transcription factors can
reprogram old cells into
stem cells or young cells
that regenerate tissues.
Transcription factors are proteins that help turn
specific genes "on" or "off" by binding to DNA.
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
 Octamer-binding factor 4
Original 4 Yamanaka Factors that
Reversed Cell Aging in 2006
Yamanaka
Transcription Factors
OCT4
KLF4
SOX2
cMYC
Acronym “OSKM”:
c-Myelocytoatosis
SRY-box factor 2
Kruppel-like factor 4
 Octamer-binding factor 4
Original 4 Yamanaka Factors that
Reversed Cell Aging in 2006
Yamanaka
Transcription Factors
OCT4
KLF4
SOX2
cMYC
Acronym “OSKM”:
c-Myelocytoatosis
SRY-box factor 2
Kruppel-like factor 4
 Octamer-binding factor 4
Original 4 Yamanaka Factors that
Reversed Cell Aging Back in 2006
Yamanaka
Transcription Factors
OCT4
KLF4
SOX2
cMYC
Acronym “OSK”:
c-Myelocytoatosis
SRY-box factor 2
Kruppel-like factor 4
Oct4 Sox2 KLF4
OSKM Yamanaka Factors
Deliver to Old Cells
Oct4
Sox2
KLF4
KLF4
Sox2
Intermittent
OSK Expression
Partial Cell Reprogramming = Biological Age Reversal
https://sitn.hms.harvard.edu/flash/2016/resetting-aging-clock-science-age-reversal/
Induced Pluripotent Stem Cell
Maintain Youthful Cells:
*This new technique completely
bypasses loss of cellular identity
and tumorigenicity problems that
limited mass application directly
to an adult living organism, using
just the factors OSK.
OSK Yamanaka Factors
cMyc
cMyc
Improved Organ Structure & Function in Many Tissues
Prior Studies Demonstrate
Short induction of OSKM in a myocardial infarction
model (heart attack) alleviated myocardial damage
and improved cardiac function.
OSK (without M) rejuvenates retinal ganglion cells
leading to axon regeneration + vision restoration
in aged and glaucoma mice/primates.
Age-related biomarkers reversed by OSK in
kidney, liver and muscle.
What happens when
Yamanaka factors are
delivered to old mice?
March 9, 2022
“Newresearchbythe
SalkInstitutehasshown
cellularrejuvenation
therapysafelyreverses
signsofaginginmice.”
https://www.drugtargetreview.com/news/101826/scientists-have-shown-ageing-process-can-be-safely-and-effectively-reversed-in-mice/
“Scientists have shown aging process can
be safely and effectively reversed in mice”
https://www.dailymail.co.uk/sciencetech/article-10589031/Scientists-REVERSE-ageing-mice-using-cellular-rejuvenation-technique.html
• Experts injected mice with molecules called the Yamanaka transcription factors
• Treatment period of seven to 10 months was effective for restoring youthfulness
• The 'safe' treatment could one day help humans wind back their biological clock
• Partialcellreprogramminginlive(invivo)mice
• OSKM(“Yamanaka”)transcriptionfactorsused
• No toxicity or increase in cancer detected
Partial Cell Reprogramming – Safe
https://www.nature.com/articles/s43587-022-00183-2
https://www.salk.edu/news-release/cellular-rejuvenation-therapy-safely-reverses-signs-of-aging-in-mice/
TheSalk InstituteReports:
“Cellularrejuvenationtherapysafelyreversessignsofaginginmice”
March 7, 2022
• Cellreprogrammingresultsin“younger”skin.
• Lower inflammation.
• Reduced senescent-associated secretory phenotypes.
Systemic Rejuvenation in Live Mice
https://www.nature.com/articles/s43587-022-00183-2
https://www.salk.edu/news-release/cellular-rejuvenation-therapy-safely-reverses-signs-of-aging-in-mice/
FindingsReportedin Nature:
“Cellular rejuvenation therapy safely reverses signs of aging in mice”
March 7, 2022
“In both the kidneys
and skin, the
epigenetics of treated
animals more closely
resembled epigenetic
patterns seen in
younger animals.”
“they found that the mice,in many ways, resembled younger animals.”
https://www.salk.edu/news-release/cellular-rejuvenation-therapy-safely-reverses-signs-of-aging-in-mice/
Major SALK findings using Yamanka factors :
The Treatment Made The
Mice’s Cells Look Younger
https://pubmed.ncbi.nlm.nih.gov/38381405/
February 26th, 2024
Cyclic induction of OSK expression
in 2-year-old wild type mice led to:
109% increase in median remaining lifespan
Improved health relative to control mice
Profound age reversal in heart and liver
tissues assessed by DNA methylation clocks
Epigenetic age reversal in human cells that make
up 90% of outmost skin layers
Improved Frailty Index Scores
Aging increases susceptibility to adverse health
outcomes that can be measured using a frailty index.
This suggests that increased lifespan in
response to OSK induction therapy
correlated with overall better health.
OSK treated mice had significant reduction
in frailty index from 7.5 points in control
mice to 6.0 points for OSK-treated mice.
High frailty compound scores reflect increase
susceptibility to poor health outcomes.
Epigenetic Age Reversal of Human Skin Cells
Exogenous induced overexpression
of OSK in these keratinocytes led to
significant epigenetic age reversal.
Keratinocytes make up 90% of
outer most skin layers.
Keratinocytes isolated from scalp
of 65-year-old male patient to
assess effects of OSK.
Two-part AAV system employed for
systemic intracellular OSK delivery.
Remarkable 109% Extension in Median
Remaining Life in Response to OSK Expression
Control mice had 8.86 weeks of life remaining
vs. 18.5 weeks in OSK-treated group
Partial OSK reprogramming increased lifespan
and improved frailty scores in old mice.
Old mice equivalent to 77-year-old people
used to enhance human translatability.
Minimal OSK Induction = Robust Age Reversal
The 109% extension of remaining lifespan + improved
frailty index + epigenetic DNA modifications occurred…
with a fraction of the OSK dose delivered to cells.
“Remarkably, using 1/10th of the
AAV at 1.7e11 vg/mouse, we
observed robust OSK expression in
the liver, heart, and spleen of both
8-week-old and 82-week-old mice”
 Control mice having a remaining lifespan of
8.86 weeks equating to approximately
 5.09 human years.
 OSK-treated mice having a remaining 18.5 weeks
equating to approximately 10.64 human years.
 OSK-treated mice lived longer in better health.
OSK-treated old mice with 18.5 weeks of life remaining would equate to
10.64 remaining human years in mouse-to-human aging approximation:
February 26th, 2024 https://pubmed.ncbi.nlm.nih.gov/38381405/
What Does This Equate to in Human Years?
February 15th, 2024
https://www.liebertpub.com/doi/10.1089/cell.2023.0072
“Together, these results may
have important implications
for the development of partial
reprogramming interventions
to reverse age-associated
diseases in the elderly.”
“Aging is the strongest risk factor for
most common human diseases hence
it is imperative to identify antiaging
interventions to delay or even
potentially reverse the aging process.”
February 26th, 2024
“Gene Therapy-mediated Partial Reprogramming Extends
Lifespan and Reverses Age-Related Changes in Aged Mice
https://pubmed.ncbi.nlm.nih.gov/38381405/
> 2006: cell reprogramming demonstratescell rejuvenation.
> 2011: Rejuvenation inducedin very old human cells (in vitro)
> 2022: Aging partiallyreversedin live mice (independent studies)
> 2024-2027: Research to rejuvenate old monkeys & humans.
Prior biology doctrine: Cell rejuvenation not possible.
Rapid Transition of Age Reversal from
Cells to Mice to Monkeys to Humans
--> Rewriting the Rules of Biology | https://pubmed.ncbi.nlm.nih.gov/33627519
AAV9 vector (adeno-associatedvirus9)-(mouseproven)
Plasmid-based vector (turncellsintobioreactors)
Lipid nano-particles (Intramuscularorintravenous)
Chemical reprogramming (intravenous)
+Otherviralvectors/intracellulardeliverymethods
In vivo delivery methods being studied:
For transcription factors to control
longevity genes they must get inside of cells.
Transcription factors are DNA-binding
proteins that control gene expression.
Upgraded Yamanaka Cocktail Jan. 4th, 2024
Enhanced induced pluripotent
stem cell generation in 5 species
https://www.cell.com/cell-stem-cell/pdfExtended/S1934-5909(23)00402-2
Universal method for
mammalian cell reprogramming
High-quality naïve stem cells
boost regenerative potential
Improved stem cell quality
https://www.mpi-muenster.mpg.de/732121/20231222-super-sox
Improved Yamanaka factors:
SOX2 / Oct 4 or “Super SOX”
“The extra stable Sox2/Oct4 dimer drives
reprogramming more efficiently…"
January 4th, 2024
“Super-Soxcanalso improvethedevelopmental
potential of existing pluripotent stem cells…”
“For the first time, we can effortlessly (in less
than a week), produce iPS cells that are so
developmentally competent that they could
easily give rise to complete living animals.”
What’s Happened So Far in
OSK transcription factors reversed epigenetic age,
improved overall health and extended remaining lifespans
>100% in old rats…research now advancing to old monkeys.
Exosome-rich young plasma cut old rat epigenetic ages in half
and improved overall health…research now advancing to dogs.
Next steps: Replicate these findings in murine models while simultaneously
initiating OSK and young plasma research in old primates.
Young plasma reversed epigenetic aging in old rats and
increased median lifespan human equivalent of about 7 years.
1)
2)
3)
https://scitechdaily.com/turning-back-the-clock-genetic-engineers-rewire-cells-for-an-82-increase-in-lifespan
“Lifespan Extension Record Set In Yeast
Cells Using Synthetic Gene Oscillator”
“Turning Back the Clock: Genetic Engineers
Rewire Cells for an 82% Increase in Lifespan”
“Engineering longevity---design of a synthetic
gene oscillator to slow cellular aging”
“Researchers make breakthrough in quest for longer life”
Major Life Span Increase - 2023
https://www.science.org/doi/10.1126/science.add7631
https://nypost.com/2023/04/28/life-expectancy-could-grow-80-with-anti-aging-breakthrough/
https://www.genengnews.com/news/lifespan-extension-record-set-in-yeast-cells-using-synthetic-gene-oscillator/
105%LifespanExtensioninYeastUsingGeneticOscillation
Study finds yeast cell aging and death
affectedbya circuitoftwo criticalpathways.
https://www.science.org/doi/10.1126/science.add7631
Yeast were engineered to overexpress two
genes (Sir2 & HAP4) in such a way that yeast
flipped between functioning pathways.
April 27th, 2023
This genetic oscillation extended
life 105% more than normal yeast.
https://www.science.org/doi/10.1126/science.add7631
105%Lifespan ExtensionUsingGeneticOscillation
April 27th, 2023
Yeast cells engineered to overexpress two genes (Sir2 & HAP) in
a way that they consistently flip between functioning pathways.
Substantial Lifespan Increase with Modest
Gene Expression Alterations in Yeast Cells
Stem cell exhaustion is a core aspect
of the aging process. Yeast are often
used as a model of human stem cells.
https://www.science.org/doi/10.1126/science.add7631
LifespanChangeinYeast
If these results translate comparably
to humans, the average lifespan of
human stem cells could increase
105% with maximum lifespans also
increasing substantially.
This would go far in solving one of the
major documented aspects of aging.
-
| March 11th, 2024
Front Page of WSJ: “The experimental therapies Odunsi and others
are receiving, by contrast, edit their cells inside their bodies. “In vivo”
gene editing, as the approach is called, could transform medicine.
Unparalleled Track Record
of Biomedical Innovation
First Established 1977
age-reversal.net
View this entire presentation at:
www.healincsummit.com
Atlantis Hotel – The Bahamas
April 29th, 2024
Advances from Cells
to Mice, Monkeys and Humans
Bill Faloon
Life Extension®

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Bill Faloon at Healinc Summit, 2024 in The Bahamas

  • 1. www.healincsummit.com Atlantis Hotel – The Bahamas April 29th, 2024 Age Reversal Advances from Cells to Mice, Monkeys and Humans Bill Faloon Life Extension®
  • 2. Decades Track Record Available at: https://www.lifeextension.com/about/life-extension-story/history 1981 1985 1986 1992 1983
  • 3. June 12, 2018 has pursued immortality for decades. Now he's got lots of company. What does https://www.popsci.com/forever-man-immortality-science/ June12,2018
  • 4. https://www.technologyreview.com/magazine/2019/09 September 2019 “Later this year, at a conference of longevity enthusiasts called RAADfest, to be held in Las Vegas, Bill Faloon plans to take the strategy one step further with what he has been calling the “Perpetual Clinical Trial.” “OLD AGE IS OVER!”
  • 5. February 28, 2021 https://www.aging-us.com/article/202712/text “When cells were reprogrammed with a 6-factor cocktail the (degenerative) alterations were fully reversed and cells fully rejuvenated.” This 2021 published review summarized age-reversal impact of cell reprogramming. Funded by Bill Faloon’s group + other charitable donors.
  • 6. April 8th, 2023 “First anti-aging pills to hit shelves in 2028, expert predicts – as Silicon Valley races to conquer death” ChatGPT boss Sam Altman has invested $180 million in anti-aging biotech firm. Long line of Silicon Valley billionaires throw considerable wealth behind the science. Jeff Bezos put $3 billion into anti-aging startup. Pills to help people reverse the effects of aging “could be on the market in the next 5 years” https://www.dailymail.co.uk/sciencetech/article-11844303 SamAltman
  • 7. “Mr. Kurzweil believes we may achieve immortality as soon as 2030, thanks to the development of ‘nanobots,’ tiny robots that will constantly repair our bodies at the cellular level. He predicts people will soon be able to eat whatever they want and stay trim while nanobots in their bodies cure diseases, create immunities and heal injuries.” | May 2nd, 2023 www.wsj.com/articles/immortality-isnt-all-its-cracked-up-to-be-nanobots-science-health-death-penalty-healthcare-33ae5abf “Even if this fantastical breakthrough becomes reality, is human immortality a good thing?” “ ” “ ”
  • 8. - May 19th, 2023 technologyreview.com/2023/05/19/1073374/i-just-met-the-founders-of-a-would-be-longevity-state/ “I just met the founders of a would-belongevity state” “What if I told you there’s a group of people who think death is morally bad…Who seek to create a new state with its own laws that expedite the development of longevity drugs, partly by encouraging biohacking and self- experimentation?”
  • 9. | July 10th, 2023 https://www.wsj.com/articles/longevity-clinics-aging-living-longer-2b98e773 “The Longevity Clinic Will See You Now…” “The clinics cater to a growing number of people obsessed with fighting aging” “ThecenterscapitalizeonAmericans’ obsessionwith livinglongeranddesireforpersonalizedmedicalcare.” “They are often wealthy people in their 40s to 60s who are seeing signs of aging.” “Venture-capital investment in longevity clinics more than doubled between 2021 and 2022, from $27 million to $57 million globally.”
  • 10. Singapore Opens World’s First Healthy Longevity Clinic in a Hospital August 31, 2023 The Healthy Longevity Clinic at Alexandra Hospital is partnering with National University of Singapore to: Optimize health and reduce burden of age-related disease Test evidence-based treatments including repurposed drugs Conduct clinical research on new longevity technologies https://www.lifespan.io/news/singapore-opens-worlds-first-healthy-longevity-clinic
  • 11. Healthy Longevity Clinic – Singapore to rigorously test clinical efficacy-/safety of: Per an Email to William Faloon from Healthy Longevity Clinic - Nov. 6, 2023 “The human research model combines evidence-based interventions with personalized medicine, remote monitoring, and health coaching. Evaluation criteria include clinical outcomes, cost-effectiveness, implementation research, and stakeholder satisfaction.” 1. Rapamycin - Early 2024 2. Taurine - Mid 2024 3. Glycine - Mid 2024 4. NMN - Mid 2024
  • 12. August 2nd, 2023 “There's one major key to unlocking extreme longevity.” “If humans living for 1,000 years seems like a complete stretch, aging expert João Pedro de Magalhães will do you one better: how about humans living for 20,000 years?” https://www.popularmechanics.com/science/health/a44713943/humans-can-live-20000-years-aging-expert/ “An Aging Expert Thinks Humans Can Live for 20,000 Years. He's Not Crazy.”
  • 13. Aging is Now Optional w/ David Sinclair | EP#60 | youtube.com/watch?v=Jk_GcwkfJGs Peter Diamandis Interviews David Sinclair David Sinclair, heads the Sinclair Lab, a Harvard lab working on a cure for aging. “I know there isn’t, it’s not even a question really.” When asked, is there is an upper limit to human aging? He responds: Aug 24, 2023
  • 14. | September 1st, 2023 Saudi’s allocated> $1 billion a yearto developtreatmentsforaging. “Saudi Arabia Is Dangling Billions for Research on Aging. Scientists Are Lining Up to Take It.” Since the Saudi foundation’s start in July 2022, it has dispersed less than $20 million. They expect to ramp up to $1 billion as projects are selected. American Federation for Aging Research got $7.76 million. U of Pittsburgh got $375k for a senescence study. Norn Group, U.S. nonprofit received $7 million. Grants thus far:
  • 16. The Economist Dedicates an Entire Issue to Age Reversal https://www.economist.com/technology-quarterly/2023-09-30
  • 20. This dosing regimen is practical for humans & a primate study is being designed using same exosome-rich young plasma fraction. “Cuts old age in half” https://link.springer.com/article/10.1007/s11357-023-00980-6/ February 2024 Intriguing dosing schedule: Exosome-rich young plasma fraction infused IV (tail) every other day for 8 days. 95 days later repeat once Exosome-Rich Young Plasma Fraction Treatment Protocol
  • 21. Plasma Fraction Reverses Epigenetic Age Liver: 74.6% Blood: 64.3% Heart: 46.5% Brain: 24.4% (hypothalamus) February, 2024 Refined Exosome Concentrate Horvath, S., Singh, K., Raj, K. et al. Reversal of biological age in multiple rat organs by young porcine plasma fraction. GeroScience 46, 367–394 (2024). https://doi.org/10.1007/s11357-023-00980-6 Average DNAm age reduced as much as 67.4% Two-year-old rats (circa 60-year-old humanage) treated with “exosome fraction of plasma” from young adult pigs reduced epigenetic age by:
  • 24. Beneficial Reductions in Epigenetic Age https://link.springer.com/article/10.1007/s11357-023-00980-6 February 2024 In young plasma-treated old rats, epigenetic ages of blood, liver, and heartreduced to levels… “comparable with young rats.”
  • 27. Restoration of Youthful Kidney Function Markers https://link.springer.com/article/10.1007/s11357-023-00980-6/figures/3 February 2024  Note creatinine levels returned to young, healthy ranges 150 days posttreatment.  This indicates potential of reversing chronic kidney disease.
  • 28. Young Plasma Research Projects Volumesofpublishedstudiesdescriberejuvenationeffectsofyoungplasma.* Several protocols under study, including periodic healthy young plasma infusions or removing senile blood proteins via apheresis with albumin/immunoglobulin or healthy young plasma replacement. *References on the following slides Projects in planning to assess effects of healthy young plasma regenerative potential in kidney, heart, liver, & brains of old humans. Young human plasma already found to regenerate brains of old rats.
  • 29. Published Reports Describing Regenerative Potential of Young Plasma Preclinical Assessment of Young Blood Plasma for Alzheimer Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172595/ The Plasma for Alzheimer Symptom Amelioration (PLASMA) Study (PLASMA) https://clinicaltrials.gov/study/NCT02256306 A randomized, controlled clinical trial of plasma exchange with albumin replacement for Alzheimer's disease: Primary results of the AMBAR Study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984263/ The Stanford Parkinson's Disease Plasma Study (SPDP) https://clinicaltrials.gov/study/NCT02968433
  • 30. Safety, Tolerability, and Feasibility of Young Plasma Infusion in the Plasma for Alzheimer Symptom Amelioration Study: A Randomized Clinical Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439869/ Preclinical Assessment of Young Blood Plasma for Alzheimer Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172595/ Young Blood Plasma Administration to Fight Alzheimer's Disease? https://www.liebertpub.com/doi/10.1089/rej.2017.1940 Platelet factors attenuate inflammation and rescue cognition in ageing https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468395/ Young blood plasma reduces Alzheimer's disease-like brain pathologies and ameliorates cognitive impairment in 3×Tg-AD mice https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278124/ Plasma-Based Strategies for Therapeutic Modulation of Brain Aging https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694331/ Young Plasma Studies Continued…
  • 31. Young Plasma Studies Continued… Aging and age-related diseases with a focus on therapeutic potentials of young blood/plasma https://link.springer.com/article/10.1007/s00210-023-02657-5 Circulating plasma factors involved in rejuvenation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746393/ Plasma from Young Rats Injected into Old Rats Induce Antiaging Effects https://www.liebertpub.com/doi/10.1089/rej.2020.2354 The effect of aging on the bone healing properties of blood plasma https://www.injuryjournal.com/article/S0020-1383(21)00426-5/fulltext Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522807/ Undulating changes in human plasma proteome profiles across the lifespan https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062043/ Young Plasma Rejuvenates Blood Dna Methylation Profile, Extends Mean Lifespan And Improves Physical Appearance In Old Rats https://pubmed.ncbi.nlm.nih.gov/38430547/
  • 32. This dosing regimen is practical for humans & a primate study is being designed using same exosome-rich young plasma fraction. “Cuts old age in half” https://link.springer.com/article/10.1007/s11357-023-00980-6/ February 2024 Intriguing dosing schedule: Exosome-rich young plasma fraction infused IV (tail) every other day for 8 days. 95 days later repeat once Exosome-Rich Young Plasma Fraction Treatment Protocol
  • 34. Young Plasma Increases Median Lifespan Beginning at age 25.6 months,one rat group given young plasma every other week until death. Beginning human equivalent of 60-65 years March 2, 2024 Survival curve of no treatment group began to decline at 26 months. From age 26 to 30 months, none of the young plasma animals died. The same age control group received no treatment. https://pubmed.ncbi.nlm.nih.gov/ 38430547/
  • 35. Significant 9.1% improvement in median lifespan of the young plasma treated group (red) compared with no treated controls (black).
  • 36. DNA methylation testing measures epigenetic age and is considered the most accurate method of assessing future morbidity/mortality risk. Young Plasma Reverses Epigenetic Age Improved insulin sensitivity, better immune & metabolic health, reduced inflammation! Epigenetic age stayed consistently lower in young plasma group until natural death with indications of: DNA methylation age of young plasma-treated rats beneficially fell below the control group
  • 37. The longest-lived animal in control (no treatment) group. That’s where gene therapy can come to the rescue! Indicates young plasma can delay median death age but may not confer super longevity One interesting caveat…
  • 38. Reprogram old cells into induced pluripotent stem cells or young adult cells that can theoretically regenerate tissues forever. Yamanaka Transcription Factors –
  • 39. There are about 1500 gene regulatory transcription factors Transcription factors can reprogram old cells into stem cells or young cells that regenerate tissues. Transcription factors are proteins that help turn specific genes "on" or "off" by binding to DNA.
  • 40. 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
  • 41.  Octamer-binding factor 4 Original 4 Yamanaka Factors that Reversed Cell Aging in 2006 Yamanaka Transcription Factors OCT4 KLF4 SOX2 cMYC Acronym “OSKM”: c-Myelocytoatosis SRY-box factor 2 Kruppel-like factor 4
  • 42.  Octamer-binding factor 4 Original 4 Yamanaka Factors that Reversed Cell Aging in 2006 Yamanaka Transcription Factors OCT4 KLF4 SOX2 cMYC Acronym “OSKM”: c-Myelocytoatosis SRY-box factor 2 Kruppel-like factor 4
  • 43.  Octamer-binding factor 4 Original 4 Yamanaka Factors that Reversed Cell Aging Back in 2006 Yamanaka Transcription Factors OCT4 KLF4 SOX2 cMYC Acronym “OSK”: c-Myelocytoatosis SRY-box factor 2 Kruppel-like factor 4
  • 44. Oct4 Sox2 KLF4 OSKM Yamanaka Factors Deliver to Old Cells Oct4 Sox2 KLF4 KLF4 Sox2 Intermittent OSK Expression Partial Cell Reprogramming = Biological Age Reversal https://sitn.hms.harvard.edu/flash/2016/resetting-aging-clock-science-age-reversal/ Induced Pluripotent Stem Cell Maintain Youthful Cells: *This new technique completely bypasses loss of cellular identity and tumorigenicity problems that limited mass application directly to an adult living organism, using just the factors OSK. OSK Yamanaka Factors cMyc cMyc
  • 45. Improved Organ Structure & Function in Many Tissues Prior Studies Demonstrate Short induction of OSKM in a myocardial infarction model (heart attack) alleviated myocardial damage and improved cardiac function. OSK (without M) rejuvenates retinal ganglion cells leading to axon regeneration + vision restoration in aged and glaucoma mice/primates. Age-related biomarkers reversed by OSK in kidney, liver and muscle.
  • 46. What happens when Yamanaka factors are delivered to old mice?
  • 48. https://www.dailymail.co.uk/sciencetech/article-10589031/Scientists-REVERSE-ageing-mice-using-cellular-rejuvenation-technique.html • Experts injected mice with molecules called the Yamanaka transcription factors • Treatment period of seven to 10 months was effective for restoring youthfulness • The 'safe' treatment could one day help humans wind back their biological clock
  • 49. • Partialcellreprogramminginlive(invivo)mice • OSKM(“Yamanaka”)transcriptionfactorsused • No toxicity or increase in cancer detected Partial Cell Reprogramming – Safe https://www.nature.com/articles/s43587-022-00183-2 https://www.salk.edu/news-release/cellular-rejuvenation-therapy-safely-reverses-signs-of-aging-in-mice/ TheSalk InstituteReports: “Cellularrejuvenationtherapysafelyreversessignsofaginginmice” March 7, 2022
  • 50. • Cellreprogrammingresultsin“younger”skin. • Lower inflammation. • Reduced senescent-associated secretory phenotypes. Systemic Rejuvenation in Live Mice https://www.nature.com/articles/s43587-022-00183-2 https://www.salk.edu/news-release/cellular-rejuvenation-therapy-safely-reverses-signs-of-aging-in-mice/ FindingsReportedin Nature: “Cellular rejuvenation therapy safely reverses signs of aging in mice” March 7, 2022
  • 51. “In both the kidneys and skin, the epigenetics of treated animals more closely resembled epigenetic patterns seen in younger animals.” “they found that the mice,in many ways, resembled younger animals.” https://www.salk.edu/news-release/cellular-rejuvenation-therapy-safely-reverses-signs-of-aging-in-mice/ Major SALK findings using Yamanka factors : The Treatment Made The Mice’s Cells Look Younger
  • 52. https://pubmed.ncbi.nlm.nih.gov/38381405/ February 26th, 2024 Cyclic induction of OSK expression in 2-year-old wild type mice led to: 109% increase in median remaining lifespan Improved health relative to control mice Profound age reversal in heart and liver tissues assessed by DNA methylation clocks Epigenetic age reversal in human cells that make up 90% of outmost skin layers
  • 53. Improved Frailty Index Scores Aging increases susceptibility to adverse health outcomes that can be measured using a frailty index. This suggests that increased lifespan in response to OSK induction therapy correlated with overall better health. OSK treated mice had significant reduction in frailty index from 7.5 points in control mice to 6.0 points for OSK-treated mice. High frailty compound scores reflect increase susceptibility to poor health outcomes.
  • 54. Epigenetic Age Reversal of Human Skin Cells Exogenous induced overexpression of OSK in these keratinocytes led to significant epigenetic age reversal. Keratinocytes make up 90% of outer most skin layers. Keratinocytes isolated from scalp of 65-year-old male patient to assess effects of OSK.
  • 55. Two-part AAV system employed for systemic intracellular OSK delivery. Remarkable 109% Extension in Median Remaining Life in Response to OSK Expression Control mice had 8.86 weeks of life remaining vs. 18.5 weeks in OSK-treated group Partial OSK reprogramming increased lifespan and improved frailty scores in old mice. Old mice equivalent to 77-year-old people used to enhance human translatability.
  • 56. Minimal OSK Induction = Robust Age Reversal The 109% extension of remaining lifespan + improved frailty index + epigenetic DNA modifications occurred… with a fraction of the OSK dose delivered to cells. “Remarkably, using 1/10th of the AAV at 1.7e11 vg/mouse, we observed robust OSK expression in the liver, heart, and spleen of both 8-week-old and 82-week-old mice”
  • 57.  Control mice having a remaining lifespan of 8.86 weeks equating to approximately  5.09 human years.  OSK-treated mice having a remaining 18.5 weeks equating to approximately 10.64 human years.  OSK-treated mice lived longer in better health. OSK-treated old mice with 18.5 weeks of life remaining would equate to 10.64 remaining human years in mouse-to-human aging approximation: February 26th, 2024 https://pubmed.ncbi.nlm.nih.gov/38381405/ What Does This Equate to in Human Years?
  • 58. February 15th, 2024 https://www.liebertpub.com/doi/10.1089/cell.2023.0072 “Together, these results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly.”
  • 59. “Aging is the strongest risk factor for most common human diseases hence it is imperative to identify antiaging interventions to delay or even potentially reverse the aging process.” February 26th, 2024 “Gene Therapy-mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice https://pubmed.ncbi.nlm.nih.gov/38381405/
  • 60. > 2006: cell reprogramming demonstratescell rejuvenation. > 2011: Rejuvenation inducedin very old human cells (in vitro) > 2022: Aging partiallyreversedin live mice (independent studies) > 2024-2027: Research to rejuvenate old monkeys & humans. Prior biology doctrine: Cell rejuvenation not possible. Rapid Transition of Age Reversal from Cells to Mice to Monkeys to Humans --> Rewriting the Rules of Biology | https://pubmed.ncbi.nlm.nih.gov/33627519
  • 61. AAV9 vector (adeno-associatedvirus9)-(mouseproven) Plasmid-based vector (turncellsintobioreactors) Lipid nano-particles (Intramuscularorintravenous) Chemical reprogramming (intravenous) +Otherviralvectors/intracellulardeliverymethods In vivo delivery methods being studied: For transcription factors to control longevity genes they must get inside of cells. Transcription factors are DNA-binding proteins that control gene expression.
  • 62. Upgraded Yamanaka Cocktail Jan. 4th, 2024 Enhanced induced pluripotent stem cell generation in 5 species https://www.cell.com/cell-stem-cell/pdfExtended/S1934-5909(23)00402-2 Universal method for mammalian cell reprogramming High-quality naïve stem cells boost regenerative potential Improved stem cell quality
  • 63. https://www.mpi-muenster.mpg.de/732121/20231222-super-sox Improved Yamanaka factors: SOX2 / Oct 4 or “Super SOX” “The extra stable Sox2/Oct4 dimer drives reprogramming more efficiently…" January 4th, 2024 “Super-Soxcanalso improvethedevelopmental potential of existing pluripotent stem cells…” “For the first time, we can effortlessly (in less than a week), produce iPS cells that are so developmentally competent that they could easily give rise to complete living animals.”
  • 64. What’s Happened So Far in OSK transcription factors reversed epigenetic age, improved overall health and extended remaining lifespans >100% in old rats…research now advancing to old monkeys. Exosome-rich young plasma cut old rat epigenetic ages in half and improved overall health…research now advancing to dogs. Next steps: Replicate these findings in murine models while simultaneously initiating OSK and young plasma research in old primates. Young plasma reversed epigenetic aging in old rats and increased median lifespan human equivalent of about 7 years. 1) 2) 3)
  • 65. https://scitechdaily.com/turning-back-the-clock-genetic-engineers-rewire-cells-for-an-82-increase-in-lifespan “Lifespan Extension Record Set In Yeast Cells Using Synthetic Gene Oscillator” “Turning Back the Clock: Genetic Engineers Rewire Cells for an 82% Increase in Lifespan” “Engineering longevity---design of a synthetic gene oscillator to slow cellular aging” “Researchers make breakthrough in quest for longer life” Major Life Span Increase - 2023 https://www.science.org/doi/10.1126/science.add7631 https://nypost.com/2023/04/28/life-expectancy-could-grow-80-with-anti-aging-breakthrough/ https://www.genengnews.com/news/lifespan-extension-record-set-in-yeast-cells-using-synthetic-gene-oscillator/
  • 66. 105%LifespanExtensioninYeastUsingGeneticOscillation Study finds yeast cell aging and death affectedbya circuitoftwo criticalpathways. https://www.science.org/doi/10.1126/science.add7631 Yeast were engineered to overexpress two genes (Sir2 & HAP4) in such a way that yeast flipped between functioning pathways. April 27th, 2023 This genetic oscillation extended life 105% more than normal yeast.
  • 67. https://www.science.org/doi/10.1126/science.add7631 105%Lifespan ExtensionUsingGeneticOscillation April 27th, 2023 Yeast cells engineered to overexpress two genes (Sir2 & HAP) in a way that they consistently flip between functioning pathways.
  • 68. Substantial Lifespan Increase with Modest Gene Expression Alterations in Yeast Cells Stem cell exhaustion is a core aspect of the aging process. Yeast are often used as a model of human stem cells. https://www.science.org/doi/10.1126/science.add7631 LifespanChangeinYeast If these results translate comparably to humans, the average lifespan of human stem cells could increase 105% with maximum lifespans also increasing substantially. This would go far in solving one of the major documented aspects of aging. -
  • 69. | March 11th, 2024 Front Page of WSJ: “The experimental therapies Odunsi and others are receiving, by contrast, edit their cells inside their bodies. “In vivo” gene editing, as the approach is called, could transform medicine.
  • 70. Unparalleled Track Record of Biomedical Innovation First Established 1977
  • 72. www.healincsummit.com Atlantis Hotel – The Bahamas April 29th, 2024 Advances from Cells to Mice, Monkeys and Humans Bill Faloon Life Extension®

Editor's Notes

  1. In about 15 minutes, I am going to make an announcement that is unprecedented in the history of medical science. In fact what is being unveiled right here at RAADfest is unparalleled in the history of the human race.