Bill Faloon presents a research update on senolytic research.

1. Senolytic Update
October 3rd 2019

2. Senolytics are compounds
that selectively destroy
senescent cells.

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

4. Normal Age Mouse Senolytic Treated Mouse
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan.” Update published in: Nature. 2016 Feb 11; 530(7589): 184–189.

5. Senolytics Extend Healthy Lifespan
 Improve frailty symptoms (gait, grip strength)
 Improve kidney/liver pathologic age scores
 Improve cardiac/arterial function
 Reduce tremors and urinary incontinence
 Decrease osteoporosis
 Increase exercise endurance
 Enhance coat color appearance
 Extend healthy lifespan
Dasatinib + Quercetin
Does anyone NOT want these benefits?
Preclinical (rodent) model shows quercetin + dasatinib
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.

6. 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.”

7. Senescentcellssecretetoxicsenescence
associatedsecretoryphenotype(SASP)
May. 17, 2019
https://science.sciencemag.org/content/364/6441/636.full
“Can stimulate
neoplastic cell growth,
tumor angiogenesis,
and metastasis, thereby
promoting development
of late-life cancers.”

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

9. 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 youngerHair loss
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845101/
Untreated Senolytic Treated Starting at Mid-Age

10. 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 youngerHair 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.

11. 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 youngerHair 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

12. “We are encouraged by the safety and tolerability observed to
date in this first study of a senolytic drug in patients with
osteoarthritis. It is that experience in patients that gives us the
confidence to initiate Part B at the highest evaluated dose.”
UNITY Biotechnology, Inc. is a company developing therapeutics
to extend healthspan by slowing, halting or reversing diseases of
aging using a patented senolytic compound.
EXPANDS ONGOING PHASE 1 STUDY TO FURTHER
EVALUATE SENESCENT CELL FACTORS IN OSTEOARTHRITIS
http://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-expands-ongoing-ubx0101-phase-1-study
“A Senolytic Drug Company” Jan. 22, 2019

13. SEPTEMBER 17, 2018
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.”

14. 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/

15. 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 years in 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

16. 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

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

18. 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.”

19. 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.”

20. 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/

21.  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

22. Age-adjusted Prevalence of Obesity and Diagnosed Diabetes
Among US Adults
Diabetes
No Data < 14.0% 14.0%–17.9% 18.0%–21.9% 22.0%–25.9% > 26.0%
No Data < 4.5% 4.5%–5.9% 6.0%–7.4% 7.5%–8.9% > 9.0%
Age-Adjusted Prevalence of Obesity and
Diagnosed Diabetes Among US Adults
CDC’s Division of Diabetes Translation. United States Diabetes Surveillance System available at http://www.cdc.gov/diabetes/data
1994 2000 2015
Diabetes1994 20152000
Obesity

23. “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

24. “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.”

25. Apr. 15, 2019Senolytics 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

26. 8 Million Americans Suffer Chronic Heart Failure
Clinical trial on existing senolytic compounds urgently needed!
Senescence involving cardiomyocytes (i.e. cardiac muscle cells) appears
to be associated with age-linked fibrosis and hypertrophy of the heart.
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 from the first 2019 published study:

27. “Declining Risk of Sudden Death in Heart Failure."
New England Journal of Medicine; 2017;377(1):41-51.
Clinical trials spanning 1995 to 2014 show:
44% decline of sudden death
in heart failure patients
Sharp Decline in Heart Failure Death Rates
Leading cause of age-related death
markedly reduced in just 19 years!

28. Heart failure is
more common in
some areas of the
United States
than in others.
This map shows
the rate of death
from heart failure
by county during
2014–2016.
Deaths from Heart Failure Vary by Geography

29. https://www.hindawi.com/journals/sci/2018/8283648/
Today’s Dilemma
https://www.ncbi.nlm.nih.gov/pubmed/29020403
No treatment fully reverses damage or completely
restores cardiac function in heart failure patients.
Patients progress towards complete heart failure.
Progenitor cell restoration and renewal is a
potential solution.

30. “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.”

31. https://onlinelibrary.wiley.com/toc/14749726/2019/18/3
Senescent Cells Damage Everything
Aged‐senescent cells contribute to impaired heart regeneration
Targeting senescent cells alleviates obesity‐induced metabolic dysfunction
The eliminationof p16‐expressing cellsin oldmice, using the INK‐ATTACtransgene,
increases bone mass indicatingthat senescent cells contribute to skeletalaging.
Pharmacological clearance of senescent cells improves survival and
recovery in aged mice following acute myocardial infarction
Systemic clearance of p16INK4a‐positive senescent cells mitigates
age‐associated intervertebral disc degeneration
An early‐senescence state in aged mesenchymal stromal cells
contributes to hematopoietic stem and progenitor cell clonogenic
impairment through the activation of a pro‐inflammatory program
This is the featured research from just ONE JOURNAL ISSUE

32. Stem Cells
Bone Marrow
Progenitor Cells
Functional Cells
Healthy Cardiac Output
Where Do Cardiac Progenitor Cells Come From?

33. “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.

34. “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.8,2019British 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

35. “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."

36. Stem Cells
Bone Marrow
Progenitor Cells
Functional Cells
Healthy Cardiac Output
Where Do Cardiac Progenitor Cells Come From?

37. Cardiac Progenitor Cell Restoration
A progenitor cell differentiates into specific cell
types and is more tissue-specific than a stem cell.
Cardiac progenitor cells differentiate into
functional cells in the heart.
Progenitor cell restoration and renewal may
reverse chronic heart failure.

38. Progenitor Cell Self-Renewal and Differentiation

39. How to Get More Healthy Progenitor Cells
1) Prompt old progenitor cells to self-renew
2) Restore production of new progenitor cells
1) Multiply patient’s progenitor cells in
culture and administer back to patient.

40. Adult stem cells lose ability to repopulate tissues with functional cells
Systemic deterioration occurs as functional cells degenerate/die
Khorraminejad-Shirazi M et al., Aging and stem cell therapy: AMPK as an applicable pharmacological target for
rejuvenation of aged stem cells and achieving higher efficacy in stem cell therapy. Hematol Oncol Stem Cell Ther (2017)
 Boost cellular AMPK
 Suppress excess mTORC1
 Replenish NAD+ cell levels
 Activate sirtuin proteins
How your stem cells may be renewed:

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

42. 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)

43. Initial Data Reported
Human Senolytic Study
RAADFest-Sept 21, 2018
Two doses of dasatinib + quercetin in osteoarthritis patients:
 82% of subjectssee relief of osteoarthritispain + improved jointfunction
 Most subjects want to re-dose (after 6 months) to see better results
 Waiting for follow-up results of MRI scans of joints & aging biomarkers
(Most study subjects had severe bone-on-bone osteoarthritis)

44. Senolytic Dose Schedule
Quercetin
25 mg per kilogram of
body weight is approximately:
100 pounds = 1,125 mg
165 pounds = 1,875 mg
220 pounds = 2,500 mg
275 pounds = 3,000 mg
330 pounds = 3,750 mg
Dasatinib
2.5 mg per kilogram of
body weight is approximately:
100 pounds = 112 mg
165 pounds = 187 mg
220 pounds = 250 mg
275 pounds = 305 mg
330 pounds = 375 mg
Take first dose of quercetin/dasatinib (preferably on empty stomach) then repeat same dose one week later.
(May repeat this protocol in 6-12 months, or sooner as your doctor may direct.)
Possible side effects include: Mild flu symptoms, diarrhea, headache, fatigue for 12-24 hours.
One quercetin + dasatinib dose once a week for two weeks only (two total doses) doses)
Caution: Take in presence of qualified medical doctor in case of severe allergic reaction.
Do not engage in strenuous exercise during or for one week after the dosing schedule.

45. How to Obtain Dasatinib
Provides two doses (160 mg each dose) to be taken
one week apart for only two consecutive weeks.
Lower Cost Alternative
(Doctor’s prescription needed in either case)
For physician listing and compounding pharmacy sources: age-reversal.net
Four tablets cost $2,200 in United States
Compounding pharmacy offers dasatinib for around $225

46. Dasatinib
Potency Verified by
Independent Assay
HPLC (high-performance liquid
chromatography) testing of a Lucius Lucidas
(dasatinib) 50 mg tablet purchased from
Bonhoa, and a Sprycel dasatinib (Bristol-Myers
Squibb) 60 mg tablet purchased from the Indian
pharmacy Vea Impex against a generic (known)
quality of dasatinib acquired from Sigma (CAS:
302962-49-8), and Sprycel dasatinib (Bristol-
Myers Squibb) 20 mg from a US pharmacy.

47. https://www.sciencedirect.com/science/article/pii/S2213231716303512

48. Too Wealthy to Die at Age 65
Paul Allen, Chairman of the Seattle
Seahawks co-founded Microsoft in 1975.
Diagnosed and treated for non-Hodgkin
lymphoma in 2009. Cancer returned in
2018. He died from septic shock.
Paul Allen was philanthropist and
donated to medical research…
but did NOT make it his priority!
https://www.nytimes.com/2018/10/15/obituaries/paul-allen-dead.html
Paul Allen (1953-2018)
Net worth > $26.1 billion
Expiration date: Oct. 15, 2018

49. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-018-0608-2
• “Inhibitors of BCL-2…were shown to selectively induce
apoptosis in malignant cells…”
• “Extensively investigated…in several malignancies,
including acute leukemia, lymphomas, and solid tumors.”
• “…important role played by BCL-2 for cancer
development…made it a relevant target for…solid tumors
and hematological neoplasias”.
May 11, 2018
“BCL-2 as therapeutic target for hematological malignancies”
Journal of Hematology and Oncology
Journal of Hematology & Oncology volume 11, Article number: 65 (2018)

50. BCL-2 as therapeutic target for hematological malignancies
https://jhoonline.biomedcentral.com/articles/10.1186/s13045-018-0608-2
May 11, 2018
Case researchers discover gene that stops cancer cell proliferation
Increased resistance to apoptosis
is a key oncogenic mechanism in
several hematological
malignancies and, in many cases,
especially in lymphoid neoplasias,
has been attributed to the
upregulation of BCL-2.
Journal of Hematology and Oncology

51. Adapted from “Bcl-2 on the brink of breakthroughs in cancer treatment” by JC Reed, Cell Death and Differentiation, 2018; 25: 3-6.
Based on data available at www.clinictrials.gov, the figure indicates molecules targeting Bcl-2 family of proteins that are currently in clinical development. The sponsors of the
molecules are indicated by color, as shown at the bottom.
Molecules in clinical development that target Bcl-2 family proteins
Authors conclusion: “Bcl-2 family of proteins are now considered as promising drug targets with the potential to
provide significant advances in the standard of care for patients suffering from oncological maladies and possibly
for certain non-oncological diseases as well.”
Take home message: Since natural polyphenols from black and green tea are demonstrated to be powerful
suppressants of Bcl-2 family of proteins, their consumption for preventive reasons or for therapeutic management of
cancer in addition to a conventional medicine standard of care is recommended.

52. Publication Summary of Results Take home message
1. Inhibition of spontaneous formation of lung tumors and
rhabdomyosarcomas in A/J mice by black and green tea
Carcinogenesis. 1998;19:501–507.
Mice spontaneously developing rhabdomyosarcoma and lung cancer that were
treated with black (2%) and green (1%) tea infusions for 52 weeks had 45% and
34% lower lung tumor incidence compared to the control group that was not
treated with black and green tea. Furthermore, mice receiving black tea also had a
profound 58% decrease in rhabdomyosarcoma incidence vs. the untreated group.
Cancer develops in response to a variety of “stress-inducing”
signals. Development and progression of various cancers are
supported by different mechanisms. However, regardless of
the type of cancer, the stress that triggers it and/or the
mechanism that drives its progression, natural polyphenols
from black and green tea were demonstrated to be a powerful
suppressant of carcinogenesis in a variety of distinct animal
models of cancer.
2. Inhibition of intestinal tumorigenesis in Apcmin/+ mice by
(-)-epigallocatechin-3-gallate, the major catechin in green tea
Cancer Res. 2005;65:10623–10631.
Administration of Epigallocatechin gallate (EGCG) at doses of 0.08% or 0.16% in
drinking fluid decreased intestinal cancer formation in mice prone to developing
this type of cancer by 37% or 47%, respectively.
3. Topical applications of caffeine or (-)-epigallocatechin
gallate (EGCG) inhibit carcinogenesis and selectively
increase apoptosis in UVB-induced skin tumors in mice
Proc Natl Acad Sci U S A. 2002;99:12455–12460.
Topical applications of EGCG (6.5 mM applied 5 days a week for 18 weeks) in a
hairless mice highly prone to developing skin cancer after exposure to UVB
decreased the number of nonmalignant and malignant tumors by 55% and 66%,
respectively. EGCG increased apoptosis of the squamous cell carcinomas but had
no effect on nontumor areas of the skin.
4. Growth inhibition and regression of human prostate and
breast tumors in athymic mice by tea epigallocatechin gallate
Cancer Lett. 1995;96:239–243.
Administration of EGCG into nude mice developing prostate and breast cancers in
response to inoculation with human prostate cancer and human breast cancer
cells inhibited tumor growth.
5. Inhibition of prostate carcinogenesis in TRAMP mice by
oral infusion of green tea polyphenols
Proc Natl Acad Sci U S A. 2001;98:10350–10355.
A human achievable dose of green tea (equivalent to six cups of green tea/day)
administered orally was demonstrated to delay the onset as well as reduce the
tumor burden in mice that spontaneously develop prostate cancer.
Natural polyphenols from black and green tea
reduce incidence of several types of cancers in animal models

53. Natural polyphenols from black and green tea decrease
cancer incidence and burden in humans
Publication Summary of Results Take home message
6. Chemoprevention of human prostate cancer by oral
administration of green tea catechins in volunteers with
high-grade prostate intraepithelial neoplasia: a preliminary
report from a one-year proof-of-principle study
Cancer Res. 2006;66(2):1234–1240.
Daily consumption of 600 mg/day of green tea catechins for 12 months
reduced prostate cancer incidence 10-fold in men initially diagnosed with
high-grade prostate intraepithelial neoplasia that often progresses to prostate
cancer.
Initial human studies have provided unconvincing results for
cancer preventive activities of green and black tea
polyphenols. The activities of these natural polyphenols in the
initial clinical trials were not as strong as polyphenol anti-
cancer effects observed in animal models.
Use of improved formulations that included higher polyphenol
doses, increased purity and better bioavailability yielded
encouraging results which suggest that green and black tea
polyphenols are indeed cancer preventive in humans.
7. Green tea extracts for the prevention of metachronous
colorectal adenomas: a pilot study.
Cancer Epidemiol Biomark Prev. 2008;17:3020–3025.
Supplementation with 2.5 g of green tea extract daily for 12 months resulted
in 50% reduction in the metachronous colorectal adenoma burden.
8. Phase 2 trial of daily, oral Polyphenon E in patients with
asymptomatic, Rai stage 0 to II chronic lymphocytic
leukemia.
Cancer. 2013;119(2):363–370.
Polyphenon E with a standardized dose of EGCG (2000 mg per dose) was
administered twice daily for 6 months to patients with early stage chronic
lymphocytic leukemia (CLL). It was demonstrated that oral EGCG in the
Polyphenon E preparation was well tolerated. Furthermore, CLL patients
experienced a significant (up to 50%) reduction in palpable lymphadenopathy
and approximately 20% decrease in the absolute lymphocyte count.
9. Green tea consumption and hematologic malignancies in
Japan: the Ohsaki study
Am J Epidemiol. 2009;170(6):730–738.
A significant inverse association between green tea consumption and the risk
of hematologic malignancies was found in a large population-based cohort of
Japanese. Those who consumed >5 cups/day of green tea had a 42% lower
risk of hematologic malignancies and a 48% lower risk of lymphoid
neoplasms relative to study participants who consumed less than 1 cup/day
of green tea.

54. Publication Summary of Results Take home message
10. Inhibition of carcinogenesis by tea
Annu Rev Pharmacol Toxicol. 2002;42:25-54.
Epigallocatechin gallate (EGCG), the main and most active polyphenolic
compound from green tea, as well as other bioactive polyphenols found in
black tea such as theaflavins are being evaluated in a context of their ability to
prevent cancer cell survival in several cancer cell lines.
Cancer cell survival can be inhibited by natural
polyphenols present in green and black tea.
11. Inhibition of carcinogenesis by tea constituents
Semin Cancer Biology. 2007; 17, 395-402
12. Molecular targets for the cancer preventive activity of tea
polyphenols
Mol Carcinog. 2006;45(6):431-435.
13. Tea polyphenols prevent lung from preneoplastic lesions and
effect p53 and bcl-2 gene expression in rat lung tissues
Int J Clin Exp Pathol. 2013;6(8):1523-1531.
Consumption of 0.3% solution of green tea polyphenols profoundly decreased
carcinogen-induced lung cancer development by reducing the precancerous
lesions. The main mechanism reducing the burden of bronchial epithelial
lesions was green tea-induced suppression in Bcl-2 expression.
Natural polyphenols are anti-cancerogenic as they
inhibit cancer cell survival supported by Bcl-2 family
of proteins.
Natural polyphenols either suppress activity or
expression of Bcl-2 family of proteins, thereby
triggering cell death in cancer cells.
14. Mechanisms of cancer prevention by green and black tea
polyphenols
Anticancer Agents Med Chem. 2006;6(5):389-406.
ECGC and other green and black tea polyphenols induced cell cycle arrest,
telomere fragmentation and apoptosis in human cancer cell lines. ECGC
induced cancer cell apoptosis by inhibiting Bcl-2 activity.
15. Role of p53 and NF-kappaB in epigallocatechin-3-gallate-induced
apoptosis of LNCaP cells
Oncogene. 2003;22(31):4851-4859.
EGCG induced apoptosis in human prostate carcinoma LNCaP cell line by
decreasing the expression of Bcl-2.
16. Cancer prevention by tea polyphenols is linked to their direct
inhibition of antiapoptotic Bcl-2-family proteins
Cancer Res. 2003 Dec 1;63(23):8118-8121.
Green tea catechins and black tea theaflavins are discussed as being very
potent inhibitors of the antiapoptotic Bcl-2-family proteins, Bcl-xL and Bcl-2.
Natural polyphenols from black and green tea induce cancer cell death
via suppression of B-cell lymphoma-2 (Bcl-2) family of proteins

55. Costs about $72 a year

56. Dasatinib
Potency Verified by
Independent Assay
HPLC (high-performance liquid
chromatography) testing of a Lucius Lucidas
(dasatinib) 50 mg tablet purchased from
Bonhoa, and a Sprycel dasatinib (Bristol-Myers
Squibb) 60 mg tablet purchased from the Indian
pharmacy Vea Impex against a generic (known)
quality of dasatinib acquired from Sigma (CAS:
302962-49-8), and Sprycel dasatinib (Bristol-
Myers Squibb) 20 mg from a US pharmacy.

57. Dasatinib
C
Potency Verified by
Independent Assay
Can cost under $150 a year

58. Senolytic Dose Schedule
Quercetin
25 mg per kilogram of
body weight is approximately:
100 pounds = 1,125 mg
165 pounds = 1,875 mg
220 pounds = 2,500 mg
275 pounds = 3,000 mg
330 pounds = 3,750 mg
Dasatinib
2.5 mg per kilogram of
body weight is approximately:
100 pounds = 112 mg
165 pounds = 187 mg
220 pounds = 250 mg
275 pounds = 305 mg
330 pounds = 375 mg
Take first dose of quercetin/dasatinib (preferably on empty stomach) then repeat same dose one week later.
(May repeat this protocol in 6-12 months, or sooner as your doctor may direct.)
Possible side effects include: Mild flu symptoms, diarrhea, headache, fatigue for 12-24 hours.
One quercetin + dasatinib dose once a week for two weeks only (two total doses) doses)
Caution: Take in presence of qualified medical doctor in case of severe allergic reaction.
Do not engage in strenuous exercise during or for one week after the dosing schedule.

59. Senolytic Update
October 3rd 2019