1. “Vintage people” are possible, just like vintage cars Dr. Aubrey de Grey Methuselah Foundation, Cambridge, UK Email: aubrey@sens.org Website: http://www.sens.org/

2. Fun Not fun Why should we cure aging?

3. Q: Why then is aging defended? A: Rational denial - Aging is ghastly - Aging is inevitable It is rational to put ghastly but inevitable things out of our minds, even if we have to be amazingly irrational in order to do so. But if the inevitability becomes unclear…

4. Aging in a nutshell Metabolism (the network of molecular and cellular processes that keep us alive) eventually causes Pathology (the network of molecular and cellular processes that kill us)

5. Problem 1: this is metabolism

6. Problem 2: this is the pathology Alzheimer’s Stroke Sarcopenia Osteoarthritis Hormonal Imbalance Kidney Failure Cancer Heart Disease Diabetes Incontinence Osteoporosis Macular Degeneration Parkinson’s Pneumonia Emphysema Sex Drive … and LOTS more

7. Strategies for intervention Gerontology Geriatrics Metabolism Pathology Gerontology: no way, we know far too little Geriatrics: no way, inevitably a losing battle Conclusion: aging will defeat us for centuries Is that conclusion inescapable?

8. Aging in slightly less of a nutshell Metabolism ongoingly causes “damage” whereas Damage only eventually causes pathology This turns out to be very useful

9. Strategies for intervention Gerontology Geriatrics Metabolism Damage Pathology

10. How to make a car last 50 years -- plan A

11. How to make a car last 50 years -- plan B

12. Strategies for intervention Gerontology Engineering Geriatrics Metabolism Damage Pathology Claim: unlike the others, the engineering approach can achieve a large extension of human healthy lifespaspan quite soon

15. This is the damage No new type of damage identified since 1982! Seven Deadly Things 1.Junk - Inside Cells 2.Junk - Outside Cells 3.Cells - Too Few 4.Cells - Too Many 5.Mutations - Chromosomes 6.Mutations - Mitochondria 7.Protein Crosslinks

16. Damage rising with ageCould be reversed or made harmless by Cell loss, cell atrophyCell therapy, mainly Junk outside cellsVaccination causing internalisation Protein crosslinksLink-breaking molecules/enzymes Death-resistant cellsCell death gene therapy, vaccination Mitochondrial mutationsNuclear versions of 13 genes Junk inside cellsEnzymes from soil bacteria/fungi Nuclear [epi]mutations (only cancer matters) “WILT”: telomerase/ALT knockout plus periodic stem cell reseeding We know in great detail how to fix all of them Strategies for Engineered Negligible Senescence (SENS)

17. A tentative timeline Step one: Robust Mouse Rejuvenation (RMR) make normal two-year-old mice, expected to live one more year, actually live three more years 1)With $100m/year we have a 90% chance of achieving RMR within 10 years 2)We have a 50% chance of “robust human rejuvenation” (doubling remaining life of 55-year-olds) within 15 years after RMR

18. Age Reserve 0 0 max frail Retarding aging: benefits modest Halving rate of damage starting in middle age - doubles remaining healthspan - raises total healthspan by 20%

19. Age Reserve 0 0 max frail Comparable repair: far better Fixing half the damage starting in middle age - doubles total healthspan - raises remaining healthspan by 5-fold hard easy

20. Age Reserve 0 0 max frail Ever-improving repair: better yet Fixing half the damage, then 3/4 - not as good as doing 3/4 first time… - but better than doing 1/2 first time… hard easy very hard

21. Age Reserve 0 0 max frail Infinitely better, in fact! Fixing half the damage, then 3/4, then 7/8…. - outpaces the so-far-unfixable damage… - maintains healthspan indefinitely

22. Definition Longevity Escape Velocity (LEV): the rate at which rejuvenation therapies must improve in order to outpace the accumulation of damage that they cannot yet repair

23. Is this rate of progress plausible? Data 19031927 19491969

24. Age Reserve 0 0 max frail LEV decreases with time Fixing half the damage, then 2/3, then 3/4…. - still good enough… - just like gravitational escape velocity

25. Data

26. A sample conclusion: The first 1000-year-old is probably less than 20 years younger than the first 150-year-old