7 ms·

Why We Age, Part III: Can We Live Forever?

62 points by Mitchhhs 11y ago

reasonattlm 11y ago
If you're talking about engineered longevity and you're not talking about the brace of technologies that fall under the SENS umbrella [1], or even the Hallmarks of Aging catalog [2] then you're missing the most important part of the field. All of the meaningful advances of the future are going to emerge from repair of the causes of aging, not from tinkering with the operation of metabolism to try to recapture some fraction of the benefits of calorie restriction. Or even, hell, five times the benefit of calorie restriction. That won't move the needle far in humans. You'll be a lot healthier, but still die on much the same schedule as your parents and grandparents. It costs two billion dollars or more to push through one drug candidate for a given desired effect. Current estimates suggest you could implement the entire SENS program of rejuvenation treatments in mice for that amount of money over 10 years. Those are technologies with potentially unbound gains on healthy life span; not just slowing down aging, but actually reversing its causes. Periodic repair has no limit on the degree to which it can extend life, and is far more effective for old people than merely slowing aging. Given the options here I know what I'd rather see the research community focusing on, but getting more R&D to focus on repair over metabolic tinkering is an ongoing process of persuasion and disruption. You might look at senescent cell clearance for an example of a SENS technology that is slowly breaking into mainstream research notice. Oh so slowly. It's almost painful to watch so much time and effort being directed to old-style mine the natural world drug discovery for marginal treatments unlikely to move the needle when we're in the midst of a biotechnology revolution and so much more is possible. [1]: http://sens.org/research/introduction-to-sens-research http://sens.org/research/introduction-to-sens-research [2]: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/
- Mitchhhs 11y ago
  I completely agree with you. Trying to find a drug that can affect the complex molecular machinery in just the right way is likely not going to work. A more likely outcome is that we will find a drug that can treat a certain age-related disease by working on these pathways.
- deegles 11y ago
  Sorry if I don't articulate this well. I'm very much in favor of life extension and SENS but I get the perception that it's still a "fringe" science or maybe it's not perceived as well by the broader community. Can you speculate why there isn't more money and effort being directed to this research if it has so much potential?
  - reasonattlm 11y ago
    1) pure science changes direction very, very slowly under the best of circumstances. 2) regulation strongly constrains funding by steering it towards drug discovery. 3) people don't like being told they're doing it wrong, even when it is absolutely true. 4) the real goal of most researchers is to catalog metabolism, not to produce any way of treating aging.
  - JoshTriplett 11y ago
    1) Lack of visibility; how many people even know this research is going on, and that it's potentially close enough to not classify as science fiction? 2) A perception as "natural", together with the naturalistic fallacy. The black plague and cancer are "natural" too, but we have no qualms eradicating them; yet for some reason, people romanticize death, especially when thinking primarily about it applying to other people rather than themselves. 3) Related to that naturalistic fallacy, aging afflicts a less sympathetic group. Given a disease that strikes down the "young and healthy", or the affliction hidden behind such thoughtless and abominable phrases as "it was their time" or "natural causes", the former will tend to attract more funding. 4) In a word, spirituality, whether spoken of or otherwise. 5) Too many crackpots through history have tried to peddle life extension, creating guilt by association.
pzaich 11y ago
I've always found the social issues surrounding extending life to be chilling after reading Kurt Vonnegut's take on it in "Tomorrow and Tomorrow and Tomorrow" (http://en.wikipedia.org/wiki/Tomorrow_and_Tomorrow_and_Tomorrow_%28short_story%29 http://en.wikipedia.org/wiki/Tomorrow_and_Tomorrow_and_Tomor...). What would a future look like where there is very little room for young people to grow?
- anigbrowl 11y ago
  IT's right outside the window, it seems to me, though I'm optimistic that population growth will level off in a few years. The other problem is economic - ownership doesn't expire so in a gerontocratic society the older members will by default end up holding more and more of the wealth. Of course, one could argue that medical are in old age is a massive sink of wealth, and so anti-aging research has the possibility to mitigate that. But unless one proposes to make people immortal - which would entail massive social disruption - such advances are likely to just postpone those expenses.
- ffn 11y ago
  I agree that it's fun to imagine, but the realities of longevity is probably a lot more prosaic. Granted Jeanna Clement can spoke for 100 years and be fine, but that doesn't mean the rest of us won't get lung cancer 10 years in if we try it. So, at present, the real secret to longevity is either superior genes (which isn't mass distributable except over a great many generations, and even then, it means giving up a portion of our genetic diversity on a societal level), disciplined lifestyles (30% less caloric intake according to the article, which means you can kiss your gains and muscular physique good-bye), and some very tricky and expensive combination of advance medicine (which, in a world where there are people who still starve to death, seems rather out of reach). In addition, you have to avoid all accidents, which is entirely out of your hands. In a lot of ways, the concern over mass longevity squeezing the world to death is like the concern over AI robots who become intelligent enough to eradicate all of humanity or the gays mass-releasing gay gay-marriage-spores that make all the straight people fall out of love. It's fun to speculate, write country songs about, and produce post-apocalyptic movies around, but being seriously worried about it as a social issue is a little unrealistic.
ctdonath 11y ago
After reading Wait But Why's treatise on Graham's Number, I'm not sure I want to. http://waitbutwhy.com/2014/11/1000000-grahams-number.html http://waitbutwhy.com/2014/11/1000000-grahams-number.html ETA: the article gives a sense of vastly hugely mind-meltingly large numbers; when considering a number so staggeringly gargantuan is just an infinitesimal speck at the mere beginning of "forever", the thought of living that long becomes crushingly daunting. I suggest potential downvoters read the link first.
- nathan_f77 11y ago
  Those are some huge numbers for sure, but how does that have any bearing on whether or not you want to live forever? You should be worried about far smaller numbers that relate to the explosion of the sun, and the heat death of the universe. EDIT: Sorry, I just finished reading the article :P He talks about death briefly at the end. I still strongly disagree, and would jump at the chance to live forever, although it's definitely scary to think about. I would always want to have suicide as an option, for unexpected events such as a life in prison, or never-ending torture. The human brain is definitely not equipped to think about timescales on the order of Graham's number, but I would probably only be "human" for an infinitesimally small period of time, relatively speaking. One day someone from the future might stumble upon these comments and laugh. I hope we make it that far, as a species.
reasonattlm 11y ago
As a reminder, this is an area of medical research where you don't have to stand to one side and hope. Providing meaningful support to specific early stage research programs in rejuvenation research is well within the capabilities of most people making average developer salaries. Look at the few hundred people who joined the Methuselah Foundation's 300 [1] over the past decade, and collectively their individual contributions of $1000/yr helped to launch early SENS research and provided seed investment in Organovo, now a successful tissue engineering concern and whose founders are a steadfast part of the New Organ initiative [2]. Or look at the crowd centered around Longecity [3] who have raised $10,000 here and $20,000 there for discrete projects in aging research, ranging from exploratory laser ablation of lipofuscin (not a success, but a worthy attempt at a technology demonstration) to a SENS project to demonstrate allotopic expression in two mitochondrial genes (did quite well, thank you). Early stage research is cheap, falling over yourself cheap. Meaningful cutting edge projects can run for a few tens of thousands of dollars over six months - you just have to know who to fund. Fortunately there are good, responsible, aggressive research organizations out there like the SENS Research Foundation [3] that are coin slots for rejuvenation research and advocacy: you can be sure that money goes to good uses, funding areas of research that need unsticking and accelerating, picking those programs that have the best expectation values. You can put in a few thousand and be in good company with hundreds of other people, many from the tech industry, who have decided that it is well worth giving a small fraction of what you make each year to help ensure that when we are old there will be treatments to prevent the medical conditions that presently harm our parents and grandparents. What use is it making a good wage, enough to greatly influence the medical technology of your future, while sitting on the sidelines and doing nothing but hoping? Who else is going to make a difference if not you? You have the choice of living the same life as before, and suffering and dying in great pain at the end, or making a better future for everyone. It really seems like a no-brainer to me. There are few places where so little money can produce so great a beneficial outcome at this time. [1]: http://mfoundation.org/300 http://mfoundation.org/300 [2]: http://neworgan.org http://neworgan.org [3]: http://longecity.org http://longecity.org [4]: http://sens.org http://sens.org
CodeSheikh 11y ago
I suggest reading "The Idea Factory - The great age of American Revolution". The book talks about the experiences of all these exceptional engineers and scientists that were brought together under the umbrella of Bell Labs and as a result a plethora of technologies came out of it (digital computers, networks etc etc). What we need today is another similar revolution but in the field of bioengineering and health sciences. http://www.amazon.com/The-Idea-Factory-American-Innovation/dp/0143122797 http://www.amazon.com/The-Idea-Factory-American-Innovation/d...
110king 11y ago
Old is Gold:: When I was a kid my grandpa told me that each person has a bowl of food reserved for him by God and when you finish it you will die, so if you want to live longer eat less.
- M8 11y ago
  What about anorexia?
  - 110king 11y ago
    INHO, eat less does not exactly mean starve yourself to death.

62 points by Mitchhhs 11y ago

If you're talking about engineered longevity and you're not talking about the brace of technologies that fall under the SENS umbrella [1], or even the Hallmarks of Aging catalog [2] then you're missing the most important part of the field. All of the meaningful advances of the future are going to emerge from repair of the causes of aging, not from tinkering with the operation of metabolism to try to recapture some fraction of the benefits of calorie restriction. Or even, hell, five times the benefit of calorie restriction. That won't move the needle far in humans. You'll be a lot healthier, but still die on much the same schedule as your parents and grandparents. It costs two billion dollars or more to push through one drug candidate for a given desired effect. Current estimates suggest you could implement the entire SENS program of rejuvenation treatments in mice for that amount of money over 10 years. Those are technologies with potentially unbound gains on healthy life span; not just slowing down aging, but actually reversing its causes. Periodic repair has no limit on the degree to which it can extend life, and is far more effective for old people than merely slowing aging. Given the options here I know what I'd rather see the research community focusing on, but getting more R&D to focus on repair over metabolic tinkering is an ongoing process of persuasion and disruption. You might look at senescent cell clearance for an example of a SENS technology that is slowly breaking into mainstream research notice. Oh so slowly. It's almost painful to watch so much time and effort being directed to old-style mine the natural world drug discovery for marginal treatments unlikely to move the needle when we're in the midst of a biotechnology revolution and so much more is possible. [1]: http://sens.org/research/introduction-to-sens-research http://sens.org/research/introduction-to-sens-research [2]: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/

Mitchhhs 11y ago
I completely agree with you. Trying to find a drug that can affect the complex molecular machinery in just the right way is likely not going to work. A more likely outcome is that we will find a drug that can treat a certain age-related disease by working on these pathways.
deegles 11y ago
Sorry if I don't articulate this well. I'm very much in favor of life extension and SENS but I get the perception that it's still a "fringe" science or maybe it's not perceived as well by the broader community. Can you speculate why there isn't more money and effort being directed to this research if it has so much potential?
- reasonattlm 11y ago
  1) pure science changes direction very, very slowly under the best of circumstances. 2) regulation strongly constrains funding by steering it towards drug discovery. 3) people don't like being told they're doing it wrong, even when it is absolutely true. 4) the real goal of most researchers is to catalog metabolism, not to produce any way of treating aging.
- JoshTriplett 11y ago
  1) Lack of visibility; how many people even know this research is going on, and that it's potentially close enough to not classify as science fiction? 2) A perception as "natural", together with the naturalistic fallacy. The black plague and cancer are "natural" too, but we have no qualms eradicating them; yet for some reason, people romanticize death, especially when thinking primarily about it applying to other people rather than themselves. 3) Related to that naturalistic fallacy, aging afflicts a less sympathetic group. Given a disease that strikes down the "young and healthy", or the affliction hidden behind such thoughtless and abominable phrases as "it was their time" or "natural causes", the former will tend to attract more funding. 4) In a word, spirituality, whether spoken of or otherwise. 5) Too many crackpots through history have tried to peddle life extension, creating guilt by association.

pzaich 11y ago

I've always found the social issues surrounding extending life to be chilling after reading Kurt Vonnegut's take on it in "Tomorrow and Tomorrow and Tomorrow" (http://en.wikipedia.org/wiki/Tomorrow_and_Tomorrow_and_Tomorrow_%28short_story%29 http://en.wikipedia.org/wiki/Tomorrow_and_Tomorrow_and_Tomor...). What would a future look like where there is very little room for young people to grow?

anigbrowl 11y ago
IT's right outside the window, it seems to me, though I'm optimistic that population growth will level off in a few years. The other problem is economic - ownership doesn't expire so in a gerontocratic society the older members will by default end up holding more and more of the wealth. Of course, one could argue that medical are in old age is a massive sink of wealth, and so anti-aging research has the possibility to mitigate that. But unless one proposes to make people immortal - which would entail massive social disruption - such advances are likely to just postpone those expenses.
ffn 11y ago
I agree that it's fun to imagine, but the realities of longevity is probably a lot more prosaic. Granted Jeanna Clement can spoke for 100 years and be fine, but that doesn't mean the rest of us won't get lung cancer 10 years in if we try it. So, at present, the real secret to longevity is either superior genes (which isn't mass distributable except over a great many generations, and even then, it means giving up a portion of our genetic diversity on a societal level), disciplined lifestyles (30% less caloric intake according to the article, which means you can kiss your gains and muscular physique good-bye), and some very tricky and expensive combination of advance medicine (which, in a world where there are people who still starve to death, seems rather out of reach). In addition, you have to avoid all accidents, which is entirely out of your hands. In a lot of ways, the concern over mass longevity squeezing the world to death is like the concern over AI robots who become intelligent enough to eradicate all of humanity or the gays mass-releasing gay gay-marriage-spores that make all the straight people fall out of love. It's fun to speculate, write country songs about, and produce post-apocalyptic movies around, but being seriously worried about it as a social issue is a little unrealistic.

ctdonath 11y ago

After reading Wait But Why's treatise on Graham's Number, I'm not sure I want to. http://waitbutwhy.com/2014/11/1000000-grahams-number.html http://waitbutwhy.com/2014/11/1000000-grahams-number.html ETA: the article gives a sense of vastly hugely mind-meltingly large numbers; when considering a number so staggeringly gargantuan is just an infinitesimal speck at the mere beginning of "forever", the thought of living that long becomes crushingly daunting. I suggest potential downvoters read the link first.

nathan_f77 11y ago
Those are some huge numbers for sure, but how does that have any bearing on whether or not you want to live forever? You should be worried about far smaller numbers that relate to the explosion of the sun, and the heat death of the universe. EDIT: Sorry, I just finished reading the article :P He talks about death briefly at the end. I still strongly disagree, and would jump at the chance to live forever, although it's definitely scary to think about. I would always want to have suicide as an option, for unexpected events such as a life in prison, or never-ending torture. The human brain is definitely not equipped to think about timescales on the order of Graham's number, but I would probably only be "human" for an infinitesimally small period of time, relatively speaking. One day someone from the future might stumble upon these comments and laugh. I hope we make it that far, as a species.

reasonattlm 11y ago

As a reminder, this is an area of medical research where you don't have to stand to one side and hope. Providing meaningful support to specific early stage research programs in rejuvenation research is well within the capabilities of most people making average developer salaries. Look at the few hundred people who joined the Methuselah Foundation's 300 [1] over the past decade, and collectively their individual contributions of $1000/yr helped to launch early SENS research and provided seed investment in Organovo, now a successful tissue engineering concern and whose founders are a steadfast part of the New Organ initiative [2]. Or look at the crowd centered around Longecity [3] who have raised $10,000 here and $20,000 there for discrete projects in aging research, ranging from exploratory laser ablation of lipofuscin (not a success, but a worthy attempt at a technology demonstration) to a SENS project to demonstrate allotopic expression in two mitochondrial genes (did quite well, thank you). Early stage research is cheap, falling over yourself cheap. Meaningful cutting edge projects can run for a few tens of thousands of dollars over six months - you just have to know who to fund. Fortunately there are good, responsible, aggressive research organizations out there like the SENS Research Foundation [3] that are coin slots for rejuvenation research and advocacy: you can be sure that money goes to good uses, funding areas of research that need unsticking and accelerating, picking those programs that have the best expectation values. You can put in a few thousand and be in good company with hundreds of other people, many from the tech industry, who have decided that it is well worth giving a small fraction of what you make each year to help ensure that when we are old there will be treatments to prevent the medical conditions that presently harm our parents and grandparents. What use is it making a good wage, enough to greatly influence the medical technology of your future, while sitting on the sidelines and doing nothing but hoping? Who else is going to make a difference if not you? You have the choice of living the same life as before, and suffering and dying in great pain at the end, or making a better future for everyone. It really seems like a no-brainer to me. There are few places where so little money can produce so great a beneficial outcome at this time. [1]: http://mfoundation.org/300 http://mfoundation.org/300 [2]: http://neworgan.org http://neworgan.org [3]: http://longecity.org http://longecity.org [4]: http://sens.org http://sens.org

CodeSheikh 11y ago

I suggest reading "The Idea Factory - The great age of American Revolution". The book talks about the experiences of all these exceptional engineers and scientists that were brought together under the umbrella of Bell Labs and as a result a plethora of technologies came out of it (digital computers, networks etc etc). What we need today is another similar revolution but in the field of bioengineering and health sciences. http://www.amazon.com/The-Idea-Factory-American-Innovation/dp/0143122797 http://www.amazon.com/The-Idea-Factory-American-Innovation/d...

110king 11y ago

Old is Gold:: When I was a kid my grandpa told me that each person has a bowl of food reserved for him by God and when you finish it you will die, so if you want to live longer eat less.

M8 11y ago
What about anorexia?
- 110king 11y ago
  INHO, eat less does not exactly mean starve yourself to death.