SlideShare uma empresa Scribd logo
1 de 37
The feasibility and desirability of indefinite youth: recent advances from unexpected quarters Aubrey de Grey Department of Genetics, University of Cambridge Email: ag24@gen.cam.ac.uk Website: http://www.gen.cam.ac.uk
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
FAQ #1: What is your big idea?
Aging in a nutshell Metabolism  (the  hugely messy  network of homeostatic processes that keep us alive) causes Pathology  (the  hugely messy  network of antihomeostatic processes that kill us) This is not controversial  -- indeed, it is why most biogerontologists think there’s little hope of curing aging for ages
A very simple observation Aging is indisputably a side-effect of essential biochemical and cellular processes BUT Its functional effect (loss of performance) is  delayed Putting it another way: Being alive must have  immediate  side-effects, since metabolically active molecules are short-lived BUT Those effects must  accumulate , and have a  threshold  level below which they are harmless
Aging in slightly less of a nutshell Metabolism  ongoingly  causes damage whereas Damage only  eventually  causes pathology This turns out to be very useful
Three paradigms for intervention Gerontology  Engineering  Geriatrics Metabolism  Damage  Pathology Claim:  only the “engineering” approach can achieve substantial extension of human healthspan any time soon
FAQ #2: That’s all a bit abstract and theoretical, innit?
 
 
FAQ #3: Yes, but that’s just an analogy: why believe it?
Metabolism  Damage   Pathology: The seven deadly things Neurodegeneration Atherosclerosis Cancer Diabetes Hormone decline Blindness Immune decline Etc, etc, etc Cell loss/atrophy Nuclear mutations  and epimutations mtDNA mutations Senescent cells AGE crosslinks Extracellular junk Lysosomal junk Er.... that’s it! Respiration (oxidation) Carbohydrate metabolism (glycation) Cell turnover (mutations,  telomere  shortening,  dysregulation,  stem cell  depletion) Etc, etc, etc
FAQ #4: How do you know this list is complete?
20 years is an instructively long time to find nothing out Harman (1972) Mitoch. mutations Strehler (1959) or earlier Lysosomal junk Brody (1955) or earlier Cell loss, cell atrophy Hayflick (1965) Senescent cells Alzheimer (1907) Extracellular junk Monnier and Cerami (1981) Extracellular crosslinks Szilard (1959) and Cutler (1982) Nuclear [epi]mutations (only cancer matters) Proposed as contributing to aging by Damage rising w/ age
20 years is an instructively long time to find nothing out Harman (1972) Mitoch. mutations Strehler (1959) or earlier Lysosomal junk Brody (1955) or earlier Cell loss, cell atrophy Hayflick (1965) Senescent cells Alzheimer (1907) Extracellular junk Monnier and Cerami (1981) Extracellular crosslinks Szilard (1959) and Cutler (1982) Nuclear [epi]mutations (only cancer matters) Proposed as contributing to aging by Damage rising w/ age
Mitochondrial biogenesis: ripe for tweaking de Grey 2000,  Trends in Biotechnology  18:394-399
Is it really that easy?  No, but.... Gearing  1986 : one small protein relocated in yeast Nagley  1988 : shown to be functional Galanis  1991 : a second small protein relocated in yeast Lander/Lodish  1990 : suggestion of therapeutic potential Zullo  2000  (after 9 years): one big protein in rodent cells Manfredi  2001  (after 6 years): same one in human cells Guy  2002  (after 1 year): a different one in human cells
 
Clues from very unexpected quarters 1990 :  Chlamydomonas reinhardtii  mito. genome sequenced SIX  of the “dirty baker’s dozen” missing! Feb 1998:  NONE  cloned; AdG starts complaining about this July 1998: King/Gonzalez-Halphen collaboration begins ~2001:  C. reinhardtii  COX2, COX3, ATP6, ND4L cloned 2002:  C.r.   ATP6 found to work unaltered in human cells 1991 :  Vigna radiata  COX2 cloned 2002: importability found to depend on  TWO  a.a. changes
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
A taster of tomorrow’s talk -  Lysosomal junk causes atherosclerosis, macular degeneration and most -- if not all -- forms of neurodegeneration - It accumulates because we lack enzymes to break it down - Such enzymes seem to exist in some soil bacteria! - As with plant mitochondrial genes, these can in principle be exploited therapeutically
Desirability Convincing the world that aging is bad: futile until we really rejuvenate mice?
Desirability breaking the global trance
Trance? Consider some standard excuses for condemning 100,000 people to death, every day, forever: “ Wouldn’t it be crushingly boring?” “ How would we pay the pensions?” “ What about starving African children?” “ Dictators would rule forever!” Claim:  nobody is really that dumb -- they MUST be in a trance
A heartening convert Who's Afraid of Life Extension? Harry R. Moody, Institute for Human Values in Aging International Longevity Center-USA When I began to prepare to write this article, I was clear and confident about my direction. Anti-aging technologies, I was sure, are a snare and a delusion … It is a line of thought I have held for many years … But the more I thought about my skepticism and hostility to life-extension technology, the more uneasy I became. Gradually, as I reflected on my uneasiness, I found it more and more difficult to rationalize my strong rejection of life extension.
Yes, Harry Moody said this …  within mainstream gerontology, anti-aging medicine is widely viewed with hostility and skepticism (an incipient form of “gerontological correctness”?). But we are entitled to wonder: Are the arguments against anti-aging medicine valid, or are the opponents of anti-aging medicine (including me) simply gerontological Luddites? If one lifelong opponent can wake HIMSELF up, there is hope yet…
Another unexpected ally (eventually…): the wisdom of repugnance “ Offensive.” “Grotesque.” “Revolting.” “Repugnant.” “Repulsive." These are the words most commonly heard regarding the prospect of human cloning. .... Even Dolly's creator has said he "would find it offensive" to clone a human being.  Revulsion is not an argument; and some of yesterday's repugnances are today calmly accepted -- though, one must add, not always for the better.  In crucial cases , however, repugnance is the emotional expression of deep wisdom, beyond reason's power fully to articulate. Would anybody's failure to give full rational justification for his or her revulsion at these practices make that revulsion ethically suspect? Not at all. On the contrary, we are suspicious of those who think that they can rationalize away our horror Leon Kass, 1997, “The Wisdom of Repugnance”
Why is this useful?   Fundamentally barbaric   Keeps the numbers down   Traditional Human aging Fox hunting
[object Object],[object Object],[object Object],[object Object]
Another unlikely ally in the making: A4M -  Business:   promoting “anti-aging” products -  Policy:   “open-mindedness” -- anyone can buy a stall at the expo right next to the meeting, sell magnetic water or whatever, and they do -  Interpretation:   profit first, efficacy second -  Resulting reputation:   oiliest of the snakes
My abstract, intro at the A4M-funded Singapore conference 6 weeks ago “ Anti-aging medicine does not currently exist, in the sense in which the term ‘medicine’ is generally used. Medicine is biomedical technology that, at least for most recipients,  effectively  treats the  primary  symptoms of the condition against which it is claimed to act. The primary symptom of aging is indisputably death, and no existing product appreciably delays death from aging.” And what happened?
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
The rational theist Points to be carefully noted: 1) Fundamentalists (very numerous, very powerful) do, in the end, follow the doctrine as it evolves 2) God deprecates hastening death, however good the afterlife is claimed to be 3) God also deprecates apathy The most invulnerable to the life-extension crusade is “Yes, we should cure aging ASAP, but I don’t feel like it”
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Let’s  roll [email_address] http://www.gen.cam.ac.uk/sens/ http://www.methuselahmouse.org/

Mais conteúdo relacionado

Semelhante a 香港六合彩

Anti-aging supplements? Myths, reality and speculation
Anti-aging supplements? Myths, reality and speculationAnti-aging supplements? Myths, reality and speculation
Anti-aging supplements? Myths, reality and speculationUKH+
 
Life Extension an Enhancement
Life Extension an EnhancementLife Extension an Enhancement
Life Extension an EnhancementDanila Medvedev
 
Longevity and skincare – the connection
Longevity and skincare – the connectionLongevity and skincare – the connection
Longevity and skincare – the connectionDavid Christensen
 
Ageing #scichallenge2017
Ageing  #scichallenge2017Ageing  #scichallenge2017
Ageing #scichallenge2017Vlad Ghenu
 
William Faloon on Age Reversal
William Faloon on Age ReversalWilliam Faloon on Age Reversal
William Faloon on Age ReversalAlex Vidal
 
香港六合彩
香港六合彩香港六合彩
香港六合彩wejia
 
Aging vs agings: limits and consequences of biomedical definitions
Aging vs agings: limits and consequences of biomedical definitionsAging vs agings: limits and consequences of biomedical definitions
Aging vs agings: limits and consequences of biomedical definitionsattilacsordas
 
what is life and scientific method (talk1)
what is life and scientific method (talk1)what is life and scientific method (talk1)
what is life and scientific method (talk1)Nutjuda Ratchakrut
 
Research Ethics 20th Nov 09 Arec
Research Ethics 20th Nov 09 ArecResearch Ethics 20th Nov 09 Arec
Research Ethics 20th Nov 09 ArecColin_Standfield
 
Organ cloning jarrett morley
Organ cloning jarrett morleyOrgan cloning jarrett morley
Organ cloning jarrett morleyMorganScience
 

Semelhante a 香港六合彩 (15)

Anti-aging supplements? Myths, reality and speculation
Anti-aging supplements? Myths, reality and speculationAnti-aging supplements? Myths, reality and speculation
Anti-aging supplements? Myths, reality and speculation
 
Life Extension an Enhancement
Life Extension an EnhancementLife Extension an Enhancement
Life Extension an Enhancement
 
Longevity and skincare – the connection
Longevity and skincare – the connectionLongevity and skincare – the connection
Longevity and skincare – the connection
 
Symposium2015 kyriazis
Symposium2015 kyriazisSymposium2015 kyriazis
Symposium2015 kyriazis
 
SENS Article
SENS ArticleSENS Article
SENS Article
 
Ageing #scichallenge2017
Ageing  #scichallenge2017Ageing  #scichallenge2017
Ageing #scichallenge2017
 
Working Thesis
Working ThesisWorking Thesis
Working Thesis
 
William Faloon on Age Reversal
William Faloon on Age ReversalWilliam Faloon on Age Reversal
William Faloon on Age Reversal
 
Junior paper
Junior paperJunior paper
Junior paper
 
香港六合彩
香港六合彩香港六合彩
香港六合彩
 
Aging vs agings: limits and consequences of biomedical definitions
Aging vs agings: limits and consequences of biomedical definitionsAging vs agings: limits and consequences of biomedical definitions
Aging vs agings: limits and consequences of biomedical definitions
 
what is life and scientific method (talk1)
what is life and scientific method (talk1)what is life and scientific method (talk1)
what is life and scientific method (talk1)
 
Research Ethics 20th Nov 09 Arec
Research Ethics 20th Nov 09 ArecResearch Ethics 20th Nov 09 Arec
Research Ethics 20th Nov 09 Arec
 
Lessons_of_the_past
Lessons_of_the_pastLessons_of_the_past
Lessons_of_the_past
 
Organ cloning jarrett morley
Organ cloning jarrett morleyOrgan cloning jarrett morley
Organ cloning jarrett morley
 

Mais de shujia

香港六合彩
香港六合彩香港六合彩
香港六合彩shujia
 
香港六合彩
香港六合彩香港六合彩
香港六合彩shujia
 
香港六合彩
香港六合彩香港六合彩
香港六合彩shujia
 
香港六合彩
香港六合彩香港六合彩
香港六合彩shujia
 
香港六合彩
香港六合彩香港六合彩
香港六合彩shujia
 
香港六合彩
香港六合彩香港六合彩
香港六合彩shujia
 

Mais de shujia (6)

香港六合彩
香港六合彩香港六合彩
香港六合彩
 
香港六合彩
香港六合彩香港六合彩
香港六合彩
 
香港六合彩
香港六合彩香港六合彩
香港六合彩
 
香港六合彩
香港六合彩香港六合彩
香港六合彩
 
香港六合彩
香港六合彩香港六合彩
香港六合彩
 
香港六合彩
香港六合彩香港六合彩
香港六合彩
 

Último

Axa Assurance Maroc - Insurer Innovation Award 2024
Axa Assurance Maroc - Insurer Innovation Award 2024Axa Assurance Maroc - Insurer Innovation Award 2024
Axa Assurance Maroc - Insurer Innovation Award 2024The Digital Insurer
 
🐬 The future of MySQL is Postgres 🐘
🐬  The future of MySQL is Postgres   🐘🐬  The future of MySQL is Postgres   🐘
🐬 The future of MySQL is Postgres 🐘RTylerCroy
 
TrustArc Webinar - Unlock the Power of AI-Driven Data Discovery
TrustArc Webinar - Unlock the Power of AI-Driven Data DiscoveryTrustArc Webinar - Unlock the Power of AI-Driven Data Discovery
TrustArc Webinar - Unlock the Power of AI-Driven Data DiscoveryTrustArc
 
Boost PC performance: How more available memory can improve productivity
Boost PC performance: How more available memory can improve productivityBoost PC performance: How more available memory can improve productivity
Boost PC performance: How more available memory can improve productivityPrincipled Technologies
 
Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...
Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...
Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...Miguel Araújo
 
A Domino Admins Adventures (Engage 2024)
A Domino Admins Adventures (Engage 2024)A Domino Admins Adventures (Engage 2024)
A Domino Admins Adventures (Engage 2024)Gabriella Davis
 
HTML Injection Attacks: Impact and Mitigation Strategies
HTML Injection Attacks: Impact and Mitigation StrategiesHTML Injection Attacks: Impact and Mitigation Strategies
HTML Injection Attacks: Impact and Mitigation StrategiesBoston Institute of Analytics
 
presentation ICT roal in 21st century education
presentation ICT roal in 21st century educationpresentation ICT roal in 21st century education
presentation ICT roal in 21st century educationjfdjdjcjdnsjd
 
Finology Group – Insurtech Innovation Award 2024
Finology Group – Insurtech Innovation Award 2024Finology Group – Insurtech Innovation Award 2024
Finology Group – Insurtech Innovation Award 2024The Digital Insurer
 
Apidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, Adobe
Apidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, AdobeApidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, Adobe
Apidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, Adobeapidays
 
GenCyber Cyber Security Day Presentation
GenCyber Cyber Security Day PresentationGenCyber Cyber Security Day Presentation
GenCyber Cyber Security Day PresentationMichael W. Hawkins
 
Handwritten Text Recognition for manuscripts and early printed texts
Handwritten Text Recognition for manuscripts and early printed textsHandwritten Text Recognition for manuscripts and early printed texts
Handwritten Text Recognition for manuscripts and early printed textsMaria Levchenko
 
Tata AIG General Insurance Company - Insurer Innovation Award 2024
Tata AIG General Insurance Company - Insurer Innovation Award 2024Tata AIG General Insurance Company - Insurer Innovation Award 2024
Tata AIG General Insurance Company - Insurer Innovation Award 2024The Digital Insurer
 
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemkeProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemkeProduct Anonymous
 
How to Troubleshoot Apps for the Modern Connected Worker
How to Troubleshoot Apps for the Modern Connected WorkerHow to Troubleshoot Apps for the Modern Connected Worker
How to Troubleshoot Apps for the Modern Connected WorkerThousandEyes
 
TrustArc Webinar - Stay Ahead of US State Data Privacy Law Developments
TrustArc Webinar - Stay Ahead of US State Data Privacy Law DevelopmentsTrustArc Webinar - Stay Ahead of US State Data Privacy Law Developments
TrustArc Webinar - Stay Ahead of US State Data Privacy Law DevelopmentsTrustArc
 
Data Cloud, More than a CDP by Matt Robison
Data Cloud, More than a CDP by Matt RobisonData Cloud, More than a CDP by Matt Robison
Data Cloud, More than a CDP by Matt RobisonAnna Loughnan Colquhoun
 
From Event to Action: Accelerate Your Decision Making with Real-Time Automation
From Event to Action: Accelerate Your Decision Making with Real-Time AutomationFrom Event to Action: Accelerate Your Decision Making with Real-Time Automation
From Event to Action: Accelerate Your Decision Making with Real-Time AutomationSafe Software
 
Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...
Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...
Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...Drew Madelung
 

Último (20)

Axa Assurance Maroc - Insurer Innovation Award 2024
Axa Assurance Maroc - Insurer Innovation Award 2024Axa Assurance Maroc - Insurer Innovation Award 2024
Axa Assurance Maroc - Insurer Innovation Award 2024
 
🐬 The future of MySQL is Postgres 🐘
🐬  The future of MySQL is Postgres   🐘🐬  The future of MySQL is Postgres   🐘
🐬 The future of MySQL is Postgres 🐘
 
TrustArc Webinar - Unlock the Power of AI-Driven Data Discovery
TrustArc Webinar - Unlock the Power of AI-Driven Data DiscoveryTrustArc Webinar - Unlock the Power of AI-Driven Data Discovery
TrustArc Webinar - Unlock the Power of AI-Driven Data Discovery
 
Boost PC performance: How more available memory can improve productivity
Boost PC performance: How more available memory can improve productivityBoost PC performance: How more available memory can improve productivity
Boost PC performance: How more available memory can improve productivity
 
Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...
Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...
Mastering MySQL Database Architecture: Deep Dive into MySQL Shell and MySQL R...
 
A Domino Admins Adventures (Engage 2024)
A Domino Admins Adventures (Engage 2024)A Domino Admins Adventures (Engage 2024)
A Domino Admins Adventures (Engage 2024)
 
HTML Injection Attacks: Impact and Mitigation Strategies
HTML Injection Attacks: Impact and Mitigation StrategiesHTML Injection Attacks: Impact and Mitigation Strategies
HTML Injection Attacks: Impact and Mitigation Strategies
 
presentation ICT roal in 21st century education
presentation ICT roal in 21st century educationpresentation ICT roal in 21st century education
presentation ICT roal in 21st century education
 
Finology Group – Insurtech Innovation Award 2024
Finology Group – Insurtech Innovation Award 2024Finology Group – Insurtech Innovation Award 2024
Finology Group – Insurtech Innovation Award 2024
 
Apidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, Adobe
Apidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, AdobeApidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, Adobe
Apidays New York 2024 - Scaling API-first by Ian Reasor and Radu Cotescu, Adobe
 
GenCyber Cyber Security Day Presentation
GenCyber Cyber Security Day PresentationGenCyber Cyber Security Day Presentation
GenCyber Cyber Security Day Presentation
 
+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUDHA...
+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUDHA...+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUDHA...
+971581248768>> SAFE AND ORIGINAL ABORTION PILLS FOR SALE IN DUBAI AND ABUDHA...
 
Handwritten Text Recognition for manuscripts and early printed texts
Handwritten Text Recognition for manuscripts and early printed textsHandwritten Text Recognition for manuscripts and early printed texts
Handwritten Text Recognition for manuscripts and early printed texts
 
Tata AIG General Insurance Company - Insurer Innovation Award 2024
Tata AIG General Insurance Company - Insurer Innovation Award 2024Tata AIG General Insurance Company - Insurer Innovation Award 2024
Tata AIG General Insurance Company - Insurer Innovation Award 2024
 
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemkeProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
ProductAnonymous-April2024-WinProductDiscovery-MelissaKlemke
 
How to Troubleshoot Apps for the Modern Connected Worker
How to Troubleshoot Apps for the Modern Connected WorkerHow to Troubleshoot Apps for the Modern Connected Worker
How to Troubleshoot Apps for the Modern Connected Worker
 
TrustArc Webinar - Stay Ahead of US State Data Privacy Law Developments
TrustArc Webinar - Stay Ahead of US State Data Privacy Law DevelopmentsTrustArc Webinar - Stay Ahead of US State Data Privacy Law Developments
TrustArc Webinar - Stay Ahead of US State Data Privacy Law Developments
 
Data Cloud, More than a CDP by Matt Robison
Data Cloud, More than a CDP by Matt RobisonData Cloud, More than a CDP by Matt Robison
Data Cloud, More than a CDP by Matt Robison
 
From Event to Action: Accelerate Your Decision Making with Real-Time Automation
From Event to Action: Accelerate Your Decision Making with Real-Time AutomationFrom Event to Action: Accelerate Your Decision Making with Real-Time Automation
From Event to Action: Accelerate Your Decision Making with Real-Time Automation
 
Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...
Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...
Strategies for Unlocking Knowledge Management in Microsoft 365 in the Copilot...
 

香港六合彩

  • 1. The feasibility and desirability of indefinite youth: recent advances from unexpected quarters Aubrey de Grey Department of Genetics, University of Cambridge Email: ag24@gen.cam.ac.uk Website: http://www.gen.cam.ac.uk
  • 2.
  • 3. FAQ #1: What is your big idea?
  • 4. Aging in a nutshell Metabolism (the hugely messy network of homeostatic processes that keep us alive) causes Pathology (the hugely messy network of antihomeostatic processes that kill us) This is not controversial -- indeed, it is why most biogerontologists think there’s little hope of curing aging for ages
  • 5. A very simple observation Aging is indisputably a side-effect of essential biochemical and cellular processes BUT Its functional effect (loss of performance) is delayed Putting it another way: Being alive must have immediate side-effects, since metabolically active molecules are short-lived BUT Those effects must accumulate , and have a threshold level below which they are harmless
  • 6. Aging in slightly less of a nutshell Metabolism ongoingly causes damage whereas Damage only eventually causes pathology This turns out to be very useful
  • 7. Three paradigms for intervention Gerontology Engineering Geriatrics Metabolism Damage Pathology Claim: only the “engineering” approach can achieve substantial extension of human healthspan any time soon
  • 8. FAQ #2: That’s all a bit abstract and theoretical, innit?
  • 9.  
  • 10.  
  • 11. FAQ #3: Yes, but that’s just an analogy: why believe it?
  • 12. Metabolism Damage Pathology: The seven deadly things Neurodegeneration Atherosclerosis Cancer Diabetes Hormone decline Blindness Immune decline Etc, etc, etc Cell loss/atrophy Nuclear mutations and epimutations mtDNA mutations Senescent cells AGE crosslinks Extracellular junk Lysosomal junk Er.... that’s it! Respiration (oxidation) Carbohydrate metabolism (glycation) Cell turnover (mutations, telomere shortening, dysregulation, stem cell depletion) Etc, etc, etc
  • 13. FAQ #4: How do you know this list is complete?
  • 14. 20 years is an instructively long time to find nothing out Harman (1972) Mitoch. mutations Strehler (1959) or earlier Lysosomal junk Brody (1955) or earlier Cell loss, cell atrophy Hayflick (1965) Senescent cells Alzheimer (1907) Extracellular junk Monnier and Cerami (1981) Extracellular crosslinks Szilard (1959) and Cutler (1982) Nuclear [epi]mutations (only cancer matters) Proposed as contributing to aging by Damage rising w/ age
  • 15. 20 years is an instructively long time to find nothing out Harman (1972) Mitoch. mutations Strehler (1959) or earlier Lysosomal junk Brody (1955) or earlier Cell loss, cell atrophy Hayflick (1965) Senescent cells Alzheimer (1907) Extracellular junk Monnier and Cerami (1981) Extracellular crosslinks Szilard (1959) and Cutler (1982) Nuclear [epi]mutations (only cancer matters) Proposed as contributing to aging by Damage rising w/ age
  • 16. Mitochondrial biogenesis: ripe for tweaking de Grey 2000, Trends in Biotechnology 18:394-399
  • 17. Is it really that easy? No, but.... Gearing 1986 : one small protein relocated in yeast Nagley 1988 : shown to be functional Galanis 1991 : a second small protein relocated in yeast Lander/Lodish 1990 : suggestion of therapeutic potential Zullo 2000 (after 9 years): one big protein in rodent cells Manfredi 2001 (after 6 years): same one in human cells Guy 2002 (after 1 year): a different one in human cells
  • 18.  
  • 19. Clues from very unexpected quarters 1990 : Chlamydomonas reinhardtii mito. genome sequenced SIX of the “dirty baker’s dozen” missing! Feb 1998: NONE cloned; AdG starts complaining about this July 1998: King/Gonzalez-Halphen collaboration begins ~2001: C. reinhardtii COX2, COX3, ATP6, ND4L cloned 2002: C.r. ATP6 found to work unaltered in human cells 1991 : Vigna radiata COX2 cloned 2002: importability found to depend on TWO a.a. changes
  • 20.
  • 21. A taster of tomorrow’s talk - Lysosomal junk causes atherosclerosis, macular degeneration and most -- if not all -- forms of neurodegeneration - It accumulates because we lack enzymes to break it down - Such enzymes seem to exist in some soil bacteria! - As with plant mitochondrial genes, these can in principle be exploited therapeutically
  • 22. Desirability Convincing the world that aging is bad: futile until we really rejuvenate mice?
  • 23. Desirability breaking the global trance
  • 24. Trance? Consider some standard excuses for condemning 100,000 people to death, every day, forever: “ Wouldn’t it be crushingly boring?” “ How would we pay the pensions?” “ What about starving African children?” “ Dictators would rule forever!” Claim: nobody is really that dumb -- they MUST be in a trance
  • 25. A heartening convert Who's Afraid of Life Extension? Harry R. Moody, Institute for Human Values in Aging International Longevity Center-USA When I began to prepare to write this article, I was clear and confident about my direction. Anti-aging technologies, I was sure, are a snare and a delusion … It is a line of thought I have held for many years … But the more I thought about my skepticism and hostility to life-extension technology, the more uneasy I became. Gradually, as I reflected on my uneasiness, I found it more and more difficult to rationalize my strong rejection of life extension.
  • 26. Yes, Harry Moody said this … within mainstream gerontology, anti-aging medicine is widely viewed with hostility and skepticism (an incipient form of “gerontological correctness”?). But we are entitled to wonder: Are the arguments against anti-aging medicine valid, or are the opponents of anti-aging medicine (including me) simply gerontological Luddites? If one lifelong opponent can wake HIMSELF up, there is hope yet…
  • 27. Another unexpected ally (eventually…): the wisdom of repugnance “ Offensive.” “Grotesque.” “Revolting.” “Repugnant.” “Repulsive." These are the words most commonly heard regarding the prospect of human cloning. .... Even Dolly's creator has said he "would find it offensive" to clone a human being. Revulsion is not an argument; and some of yesterday's repugnances are today calmly accepted -- though, one must add, not always for the better. In crucial cases , however, repugnance is the emotional expression of deep wisdom, beyond reason's power fully to articulate. Would anybody's failure to give full rational justification for his or her revulsion at these practices make that revulsion ethically suspect? Not at all. On the contrary, we are suspicious of those who think that they can rationalize away our horror Leon Kass, 1997, “The Wisdom of Repugnance”
  • 28. Why is this useful?   Fundamentally barbaric   Keeps the numbers down   Traditional Human aging Fox hunting
  • 29.
  • 30. Another unlikely ally in the making: A4M - Business: promoting “anti-aging” products - Policy: “open-mindedness” -- anyone can buy a stall at the expo right next to the meeting, sell magnetic water or whatever, and they do - Interpretation: profit first, efficacy second - Resulting reputation: oiliest of the snakes
  • 31. My abstract, intro at the A4M-funded Singapore conference 6 weeks ago “ Anti-aging medicine does not currently exist, in the sense in which the term ‘medicine’ is generally used. Medicine is biomedical technology that, at least for most recipients, effectively treats the primary symptoms of the condition against which it is claimed to act. The primary symptom of aging is indisputably death, and no existing product appreciably delays death from aging.” And what happened?
  • 32.
  • 33.
  • 34. The rational theist Points to be carefully noted: 1) Fundamentalists (very numerous, very powerful) do, in the end, follow the doctrine as it evolves 2) God deprecates hastening death, however good the afterlife is claimed to be 3) God also deprecates apathy The most invulnerable to the life-extension crusade is “Yes, we should cure aging ASAP, but I don’t feel like it”
  • 35.
  • 36.  
  • 37. Let’s roll [email_address] http://www.gen.cam.ac.uk/sens/ http://www.methuselahmouse.org/