Healthy Longevity Promotion

1. Healthy Longevity Promotion as a scientific and social task
Продление здоровой жизни как научная и социальная задача
Ilia Stambler, PhD
Vetek (Seniority) – the Movement for Longevity and Quality of Life (Israel)
International Society on Aging and Disease (ISOAD)
International Longevity Alliance (ILA)
www.longevityisrael.org
www.longevityhistory.com
www.longevityalliance.org
www.longevityforall.org
www.isoad.org
Disabled, Not
Half A Person

2. Healthy Longevity Promotion –
How? Why? Who?
• 1. Feasibility
• 2. Desirability
• 3. Action

3. 1. Feasibility:
To Achieve Healthy Longevity –
We Must Treat Degenerative Aging –
the Main Cause of Chronic Diseases and Death
The Demographic and Biomedical Case for
Late-Life Interventions in Aging
Michael J. Rae, Robert N. Butler, Judith Campisi,
Aubrey D. N. J. de Grey, Caleb E. Finch, Michael
Gough, George M. Martin, Jan Vijg, Kevin M.
Perrott, Barbara J. Logan. Science Translational
Medicine. 2 (40) 40cm21, 2010
http://stm.sciencemag.org/content/2/40/40cm21.full
Extending life: scientific prospects and political
obstacles.
Richard A. Miller. Milbank Quarterly. 80(1) 155-174,
2002
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC269009
9/

4. Aging-related diseases – the main risk factor also for
COVID-19
Zunyou Wu, Jennifer M. McGoogan JM.
Characteristics of and important lessons from the
coronavirus disease 2019 (COVID-19) outbreak in China:
summary of a report of 72 314 cases from the Chinese
Center for Disease Control and Prevention.
JAMA, 323(13):1239-1242, 2020.

5. The Pathway to Healthy Longevity:
Therapeutic intervention into aging =
Prevention of chronic aging-related disease
Feasibility proven by current research
Basic Aging Process Derivative Disease Potential Treatment
Inflammation
(“Inflammaging”)
Heart Disease, Cancer Immune-modulating substances
Cross-linkage Atherosclerosis Enzymatic oxido-reductive
depolimerization, immunoclearance
Demineralization Osteoporosis Supplementation
Loss of DNA Repair Cancer DNA Repair Enhancement
Stem cell depletion Neurodegenerative diseases Stem cell therapy
Beta Cell senescence Diabetes Cell therapy, elimination of senescent
cells
Naïve T cell depletion Susceptibility to infectious
diseases
Thymus regeneration
Selected sources – examples of research
http://www.longevityforall.org/resources/
http://www.longevityhistory.com/

6. Can we extend Healthy Longevity? Yes, we
can! Feasibility: Some sources of hope
Life expectancy increases Technology advances
Long-lived/non-aging Life-forms Experimental life-extension

7. The Pursuit of Longevity is ancient
But its scientific pursuit is young
Just about 100 years old
Elie Metchnikoff (1845 – 1916)
Cytotoxic Serum (Immunotherapy)
Probiotic Diet
Gerontology – 1903
Hormone Replacement
Therapy - 1889
www.longevityhistory.com
Charles-Édouard Brown-
Séquard (1817 – 1894)
New Therapies were developed in the study of aging and longevity

8. Feasibility: Emerging anti-aging and longevity therapeutics –
Geroprotectors
Subtraction / Detoxification
• Senolytics
(e.g. quercetin + dasatinib)
• Chelation
• Enterosorbents
• Statins
• Anti-inflammatory
(or immuno-modulating)
• Anti-glycemic
• Anti-oxidant
(incl. mitochondria-targeted)
• Anti-coagulants
Addition / Supplementation
• Cell Replacement Therapy
• Hormone Replacement Therapy
• Intra-corporeal regeneration (e.g. PGDH
inhibitors)
• Hyaluronan
• Vitamins
• Microelements
• Macroergics
• Mitochondrial modulators
• Peptide bio-regulators
Targeting “Pillars of aging”
(Based on NIH Geroscience
classification of aging targets)
1) Adaptation to Stress - e.g.
Sirtuin activators (e.g. Resvertatrol,
Pterostilbene), NAD replacement
(e.g. nicotinamide riboside - NR,
nicotinamide mononucleotide -
NMN)
2) Epigenetics - demethylating
agents, small interfering RNAs,
micronutrients
3) Inflammation - Immune-
modulating drugs (incl. anti-
inflammatories, immune checkpoint
blockade)
4) Macromolecular Damage -
Advanced Glycation Endproducts
(AGE) breakers; DNA repair
enhancing means
5) Metabolism - mTOR Inhibition
(e.g. Rapamycin / rapalogs); IGF-1
Inhibitors, Calorie-restriction
mimetics (e.g. Metformin).
6) Proteostasis – e.g. autophagy
inducers
7) Stem Cells/Regeneration – cell
therapies
Aubrey D. N. J. De Grey and Michael Rae. Ending Aging. The Rejuvenation Break-throughs That Could Reverse
Human Aging in Our Lifetime, St. Martin’s Press, New York, 2007.
Lopez-Otin Carlos, Maria A. Blasco, Linda Partridge, Manuel Serrano,and Guido Kroeme. The Hallmarks of
Aging. Cell. 153 (6) 1194–1217, 2013.
Brian K Kennedy, Shelley L. Berger, Anne Brunet, Judith Campisi, Ana Maria Cuervo, Elissa S. Epel, Claudio
Franceschi, Gordon J. Lithgow, Richard I. Morimoto, Jeffrey E. Pessin, Thomas A. Rando, Arlan Richardson, Eric E.
Schadt, Tony Wyss-Coray, and Felipe Sierra. Geroscience: Linking Aging to Chronic Disease. Cell. 159(4), 709–713,
2014.
Stambler I. Human Life Extension: Opportunities, Challenges, and Implications for Public Health Policy. In: Anti-
aging Drugs: From Basic Research to Clinical Practice. Ed. Vaiserman A, Royal Society of Chemistry, London, 2017.

9. Diagnostic evaluation measures –
To predict aging-related diseases and evaluate therapy
efficacy and safety
Candidiates for biomarkers of aging
Biological (structural) –
cellular, molecular and biochemical:
• Age-related changes in Telomere
length (Telomere measurement)
• Advanced Glycation Endproducts
(AGE-Reader)
• Biomarkers of oxidative stress
• Levels of proteins that are essential
for a critical function
• DNA repair capacity
• Decrease in one or more stem cell
populations
• T-lymphocyte subsets
• Gene expression for longevity-
associated genes, e.g. Sirtuins, Foxo,
Clotho, etc.
• Epigenetic markers (methylation)
• Measures of oxidative-reductive and
acid-base balance
Functional:
• Muscle strength (Manual muscle-testing;
Dynamometer: hand-grip strength)
• Vascular rarefaction and dysfunction
(Capillaroscopy; Blood flow techniques)
• Gait speed
• Step-to-step variability
• Balance
• Functional mobility (Timed Up and Go)
• Endurance capacity (VO2 max)
• PaO2; PaO2/FiO2
• EEG/ECG/EMG
• Nutritional state/intake
• Cognition/Geriatric Assessments
• Social participation
• Psychological type profiling (tests)
• Socio-economic status (income,
employment)

10. Leng Z, Zhu R, Hou W,..., Stambler I, …
Jin K, Zhao RC. Transplantation of
ACE2- mesenchymal stem cells
improves the outcome of patients with
COVID-19 pneumonia. Aging and
Disease, 11(2), 216-228, 2020.
https://doi.org/10.14336/AD.2020.0228
Clinical improvement by intervention into
aging-related processes

11. Our project:
Quantified Longevity Guide (QLG)
For clinical evaluation of aging, multiple aging-related diseases
(multi-morbidity) and preventive treatments
https://ec.europa.eu/eip/ageing/commitments-tracker/a3/quantified-longevity-guide-qlg_en
1) Collect massive health data (Big Data), including
diverse physiological, biochemical, metabolic, clinical,
genomic, epigenomic, functional-behavioral, socio-
economic age-related parameters.
2) Establish correlates (a.k.a. biomarkers, diagnostic
criteria) for healthy longevity vs. degenerative aging, for
the evaluation of physiological age, early diagnosis of
aging-related ill health and personalization of aging-
related and healthspan extending treatments.
3) Create a practically applicable software tool (for
physicians, research organizations, individuals) to
individually apply the established correlates and criteria,
as “The Quantified Longevity Guide – QLG”.
More data and a wider concerted R&D
effort is needed!

12. Holistic Treatments for Extending Longevity
Rest - Sleep Exercise
Moderate and Balanced Nutrition Life-affirming Attitude

13. 2. Desirability:
The ethics of healthy longevity extension
Stambler I. Ethics of Antiaging Intervention. 2019. In book:
Reference Module in Biomedical Sciences. Elsevier 2019.
Encyclopedia of Biogerontology. DOI: 10.1016/B978-0-12-
801238-3.62138-4
https://www.sciencedirect.com/science/article/pii/B9780128
012383621384
Principal
- The Ethics of Goal-Setting: Are Longevity-extending
Therapies Generally Desirable?
Practical
- The Ethics of Research and Development
- The Ethics of Therapeutic Application
- The Ethics of Distribution
- Societal and Individual Implications of Longevity-extending
Therapies
- The Ethics of Success and the Ethics of Failure

14. “Those who, on the other hand, take an optimistic view, … must
regard as conduct to be approved that which fosters life in self
and others, and as conduct to be disapproved that which
injures or endangers life in self or others…
Legislation conducive to increased longevity would, on the
pessimistic view, remain blameable; while it would be
praiseworthy on the optimistic view.”
(Herbert Spencer, 1820-1903, The Data of Ethics, 1879)
2. Desirability
Longevity Extension – Expression of the Valuation of Life

15. “It is written: ‘When you build a new house, you should make a
parapet for your roof so that you bring not bloodshed upon your
house should any man fall therefrom’ [Deut. 22:8]. …
This demonstrates, however, that there is no firmly determined time
for death. Moreover, the elimination of harmful things is efficacious in
prolonging life, whereas the undertaking of dangerous things is the
basis for shortening life.” (Maimonides, Rabbi Mosheh ben
Maimon,1135-1204, Responsum on Longevity)
Pursuit of Longevity in the Jewish Tradition
Ilia Stambler (2017) Longevity and the Jewish
tradition. In: Longevity promotion:
multidisciplinary perspectives. Longevity
History, Rishon Lezion.
http://www.longevityhistory.com/.

16. Desirability: Longevity is a
pragmatic value
• Human Development Index:
Longevity, Education, Income
(these values are correlated)

17. The ethical imperative.
Healthy Longevity – The Correlate of Wellbeing
• Longevity  The valuation of life
• Longevity  Peacefulness – A common goal for all
• Longevity  Education – A necessary condition for R&D
• Longevity  Intellectual Activity – No loss of meaning expected
• Longevity  Prosperity – No shortage of resources expected
• Longevity  “Indicator of economic success and failure” (GDP/GDP
per capital
• Longevity  Equality (Gini Index) – Healthcare inequality needs to
be addressed, equitable distribution of longevity therapies needs to
be ensured
• Longevity  Safety – Criteria for efficacy and safety of longevity
therapies need to be established.
• Stambler I, Human Life Extension: Opportunities, Challenges, and Implications for Public Health Policy. In: Anti-
aging Drugs: From Basic Research to Clinical Practice, Ed. Vaiserman A, Royal Society of Chemistry, London,
2017;
• Stambler I, The pursuit of longevity – The bringer of peace to the Middle East. Current Aging Science, 6, 25-31,
2014;
• Stambler I, Ethics of anti-ageing intervention. In: Encyclopedia of Biomedical Gerontology, Ed. Rattan S, Elsevier,
forthcoming 2020.

18. Objections to Extended Longevity
(for the Individual)
• Objections:
• Diminishing change
• Spiritual and mental
stagnation, boredom,
lack of progress and
achievement
• Prolonged suffering
• Death gives meaning
to life
• Counterarguments:
• Stability is necessary
• Potential for learning
and achievement is
increased with
increasing lifespan
• Suffering preventable
• Life has a meaning of
its own
Stambler I, Human Life Extension: Opportunities, Challenges, and Implications for
Public Health Policy. In: Anti-aging Drugs: From Basic Research to Clinical
Practice, Ed. Vaiserman A, Royal Society of Chemistry, London, 2017

19. Empirical counterarguments – No shortage
of resources due to Life Extension
“Will Malthus continue to be wrong?”
World (1963)
• Land and Food Requirements: ~550 people per square kilometer (over 700 if all the
food comes from nutritious crops); minimal food requirement ~500 kilograms dry
weight per person per year; the world dry land available for agriculture ~82 million
square kilometers
• Agricultural productivity – Yield of wheat in the UK (best in 1960) – 3,500 kg per
hectare
• Enough to feed at least 45 billion people
(The Agricultural Economics Research Institute of Oxford, Clark 1963)
• Since that time, both agricultural and industrial productivity increased
dramatically
Stambler I, The pursuit of longevity – The bringer of peace to the Middle East. Current
Aging Science, 6, 25-31, 2014
0
20
40
60
80
100
120
140
Demographic and Economic Change - UK - 1960-
2000
Life Expectancy Increase %
Population Increase %
Agricultural Productivity Increase
%
General Productivity - GDP per
Capita Increase %
0
2000
4000
6000
8000
10000
12000
Yield of Crops (kg per hectare)
UK - 1960
UK - 2000
Kuwait - 2010
Oman 2010
Demographic and economic change – UK – 1960-2000 Yield of crops – kg per hectare

20. For aging-related chronic diseases, the savings from early detection and
preventive treatment, per patient are commonly estimated at
several thousand dollars for the developed countries
 Alzheimer’s disease: $1,000 - 10,000+
 Cancer: $1,000 - 10,000+
 Heart disease: $1,000 - 10,000+
 Diabetes: $1,000 - 10,000+
Hence public support for Longevity science is warranted.
Governments should ensure the creation and implementation of policies to promote research into the
biology of aging and aging-related diseases, for improving the health and longevity of the global elderly
population. The policies should include increasing funding, incentives and institutional support for
the field.
Positive individual and social outcomes of Healthy Longevity
Rather than negative outcomes, vast humanitarian and economic benefits, for the individual and society,
are expected from early diagnosis and prevention of aging-related diseases and extension of healthy
longevity – via diagnosis and treatment of degenerative aging processes. Main benefits include savings in
healthcare, enhanced period of productivity and reduction of suffering.
Massive potential savings from early detection and prevention – Hundreds of Billions $ yearly $7.1 trillion over fifty
years, just for the US, according to Goldman et al. Substantial Health and Economic Returns from Delayed Aging May
Warrant a New Focus for Medical Research. Health Affairs, 32 (10), 1698-1705, 2013.
http://www.ncbi.nlm.nih.gov/pubmed/24101058
Stambler I, Human Life Extension: Opportunities, Challenges, and Implications for Public Health Policy. In: Anti-aging
Drugs: From Basic Research to Clinical Practice, Ed. Vaiserman A, Royal Society of Chemistry, London, 2017
The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the
Elderly Population. Kunlin Jin, James W. Simpkins, Xunming Ji, Miriam Leis, and Ilia Stambler. Aging and Disease. 6(1), 1–
5, 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306469/

21. General Need:
Goal-directed R&D to develop diagnostic and
therapeutic measures for degenerative aging –
the entire society can participate and benefit
• 1) The general public – will be encouraged to actively demand and
intelligently apply aging-ameliorating, preventive therapies.
• 2) The pharmaceutical and medical technology industry – will be
encouraged to develop and bring effective aging-ameliorating therapies
and technologies to the market.
• 3) Health insurance, life insurance and healthcare systems – will
obtain a new area for reimbursement practices, which will encourage
them and their subjects to promote healthy longevity.
• 4) Regulators and policy makers – will be encouraged to prioritize and
increase investments of public funds into aging-related research and
development.
• 5) Scientists and students – will be encouraged to tackle a
scientifically challenging and practically vital problem.

22. 3. Action
Given the Feasibility and Desirability.
What do we do?
Research, development, education,
lifestyle, advocacy, activism!

23. International level:
Policy frameworks
• ICD-10/ICD-11. “Senility/Old Age” (R54/MA20). “Failure of function of otherwise normal physiological mental or physical
process(es) by aging. Not to be used under the age of 70 years" (ICD-11 draft).
• ICD11 – “Aging-related” extension code (qualifier) XT9T "caused by pathological processes which persistently lead to
the loss of organism's adaptation and progress in older ages".
• WHO “Global Strategy and Action Plan on Ageing and Health (GSAP) - 2016-2020” (November 2015). “Strategic
objective 5: Improving measurement, monitoring and research on Healthy Ageing”. Clause “5.1: Agree on ways to
measure, analyse, describe and monitor Healthy Ageing” (Section 95).
• WHO 13th General Programme of Work (GPW) 2019-2023. “WHO will explore measuring this foundation of its work using
healthy life expectancy, which could serve as one overarching measure aligned with SDG 3” (WHO GPW13 – 2019-
2023)
• WHO Decade of Healthy Ageing (2020-2030). 4.4. Fostering research and innovation.
• “Sustainable Development Goals (SDG) - until 2030” (September 2015). Sustainable Development Goal - SDG 3
“Ensure healthy lives and promote well-being for all at all ages” -- “By 2030, reduce by one third premature mortality from
non-communicable diseases through prevention and treatment” (3.4., emphasis added). “Support the research and
development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect
developing countries, provide access to affordable essential medicines and vaccines.”
• The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
Human Use (ICH) -- “Harmonized Tripartite Guideline E7: Studies in Support of Special Populations: Geriatrics”
(recommended for adoption in the EU, US and Japan, 1993). “Drugs should be studied in all age groups, including the
elderly, for which they will have significant utility.”
• European Medicines Agency (EMA). The “Proposal for the development of a points to consider for baseline
characterisation of frailty status” including physical frailty, comorbidity status and mental frailty (May 2013).
• US Food and Drug Administration (FDA). “TAME” Study – “Targeting Aging with Metformin”. In fact – targeting
multimorbidity with metformin! (November 2015)

24. STATE LEVEL: Governments should ensure the creation and implementation of the following
policies to promote research into the biology of aging and aging-related diseases,
for improving the health and longevity of the global elderly population
ISOAD. The Critical Need to Promote Research of Aging. Aging and Disease, 6, 2015
• Funding:
• Ensuring a significant increase of governmental and non-governmental funding for goal-directed
(translational) research in preventing the degenerative aging processes, and the associated chronic
non-communicable diseases and disabilities, and for extending healthy and productive life, during
the entire life course.
• Specifically:
• Dedicating a designated percentage of budget within relevant ministries, such as ministries of health and/or
science, particularly in the divisions concerning research and treatment of non-communicable chronic
diseases.
• Dedicating a specific percentage of the profits of commercial pharmacological, biotechnology and medical technology companies to such research and development.
• Establishing relevant research grant programs on a competitive as well as goal-directed basis.
• Doubling of funding for such research every 5 years for the next 20 years.
• Incentives:
• Developing and adopting legal and regulatory frameworks that give incentives for goal-directed
research and development designed to specifically address the development, registration,
administration and accessibility of drugs, medical technologies and other therapies that will
ameliorate the aging processes and associated diseases and extend healthy life.
• Specifically:
• Developing criteria for efficacy and safety of geroprotective therapies.
• Facilitating in silico and animal testing, and ethical safety-enhanced human testing of such therapies.
• Deploying and ensuring geroprotective therapies in the status of adjuvant and life-extending therapies.
• Providing a shortened approval pathway for therapies with high level of efficacy evidence in preclinical and early clinical trials, as well as in cases of advanced degenerative
and seemingly futile conditions.
• Granting a special recognition, status and benefits to commercial and public entities engaged is such research and development.
• Institutions:
• Establishing and expanding national and international coordination and consultation structures,
programs and institutions to steer promotion of research, development and education on the
biology of aging and associated diseases and the development of clinical guidelines to modulate
the aging processes and associated aging-related diseases and to extend the healthy and
productive lifespan for the population.
• Specifically:
• Establishing Biogerontology specialty and courses in Biogerontology as a common part of
university curriculum.
• Developing and disseminating geroprotective regiments, based on the best available evidence, as part of authoritative health recommendations.
• Establishing cooperative centers of excellence for fundamental, translational and applied studies, alongside centers for strategic analysis, forecast, education and policy
development on aging and longevity research, at academic institutes and various governmental and supra-governmental agencies.

25. At the grass-root NGO level
Education and awareness: Raising public awareness about biomedical
research and development dedicated to improve healthy longevity of the
elderly population, improving the scientific, medical, social
and institutional perception of the field. Developing educational and
training materials and courses in the field, from professional to general
interest.
Communication and support: Assistance in recruiting support for the most
promising and effective diagnostic and therapeutic R&D approaches, from
specific R&D projects to establishing R&D programs and centers of
excellence. Connecting researchers in the field of biomedical research of
aging and adjacent areas and other stakeholders, by providing
capabilities for communication, consultation and cross-fertilization.
Analysis and data processing: Examination of entities active in the field,
evaluation of R&D approaches to diagnosis and treatment,
recommendations regarding the most promising R&D directions. Data
collection, curation, access, analysis, integration and sharing in the field
of aging and longevity research.

26. • Research. Educate yourself about recent advances in geroscience, as well as
its social implications.
• Study relevant fields. Including: bio-gerontology; geriatrics; biotechnology;
medical technology; social work; regenerative medicine; nano-medicine;
nutrition; ergonomics; and other fields related to geroscience.
• Join others. Discuss geroscience research with friends. Organize study groups
and live meetings. Join or start a network of supporters for geroscience on line.
Share geroscience-related information.
• Participate. Research, work, volunteer or donate for academic and public
organizations involved in geroscience.
• Lobby. Promote legislation and policies supportive of geroscience.
• Practice a healthy, life-prolonging life-style.
Promoting Healthy Longevity at the individual level:
The effort to enhance Healthy Longevity is a common goal.
Everybody can become involved and help advance Geroscience
(the science of intervention into aging to extend Healthy Longevity)
Rest - Sleep
Exercise
Nutrition Attitude

27. • Does it work? Do policy, advocacy and
activism help to advance biomedical
aging research and development?
• Some examples are positive. But more
initiatives, consultations and
experiences are needed.

28. International advocacy initiatives

29. Successful advocacy with WHO
“Ensuring healthy ageing is
an urgent challenge in all
countries” WHO 13th General
Programme of Work 2019-
2023

30. Longevity advocacy in Israel
Informing National Policy
Israel National Masterplan on Aging: Enhancing the Research,
Development and Education for the Promotion of Healthy
Longevity and Prevention of Aging-related Diseases
• 1. Increasing the R&D budget.
• 2. Increasing education.
• 3. Establishing and improving
public health systems for the
early detection and prevention
of aging-related diseases.

31. Increase support for biomedical
Research, Development and Education
for Aging and Aging-related Diseases
To improve healthy longevity of the
population