4 ms·

Delayed aging looks much harder to achieve than rejuvenation. A couple of billion dollars and ten years or so have gone into trying to just replicate the effect

Delayed aging looks much harder to achieve than rejuvenation. A couple of billion dollars and ten years or so have gone into trying to just replicate the effects of calorie restriction, in which you have state A (short-lived) and state B (long-lived) of metabolism clearly laid out for you. So far a lot has been learned, but it's clear that that is just a starting point. People in the field expect it to take decades more to get to a point of safely adjusting human metabolism to slightly slow down aging. Funnily it should be far easier to rejuvenate the old (very useful) than to slow their rate of aging (pretty useless). Aging is damage, and rejuvenation is just damage repair. See the SENS Research Foundation outline, for example. The research community already knows exactly how it could be done, since the root forms of damage that cause aging are well-enumerated, and it would only take a decade and a billion dollars to demonstrate that in mice. Full understanding isn't needed, only the understanding of what to target and how to repair it: a fraction of the knowledge needed to slow aging. Unfortunately this is a radical departure from running a drug development pipeline. The therapies look like infusions of bacterial enzymes, mitochondrial gene therapy, and more exotic things. So it remains a minority position in the research community simply because of inertia, I think - it's so much easier to raise funds when you can point to every existing Big Pharma project and say "it'll be like that." This is how incremental, expensive projects that add little value continually suck up the majority of funding in any field.

Udo 13y ago
Can you point me to some research that indicates caloric restriction leading to a higher life expectancy in humans (compared to normal nutrition, not obesity of course)?
- exratione 13y ago
  Here's a starting point to summarize thoughts on that question from some of the better known researchers involved in human studies. http://impactaging.com/papers/v5/n7/full/100581.html http://impactaging.com/papers/v5/n7/full/100581.html "Whether or not CR will extend lifespan in humans is not yet known, but accumulating data indicate that moderate CR with adequate nutrition has a powerful protective effect against obesity, type 2 diabetes, inflammation, hypertension, cardiovascular disease and reduces metabolic risk factors associated with cancer." My summary of calorie restriction research is that it (a) produces similar-ish short term changes in metabolism and measures of health in mammals tried so far, and (b) is expected to have much smaller effects on life span in humans than in mice. The present consensus is that 5 years in humans would be on the high end, as I recall. The most interesting thing to resolve with certainty in this subfield is how the short-term measures can be so similar, how the expected reduction of age-related disease in humans can be so large, and yet the life expectancy outcome be so small. Should be interesting, in a post-facto sort of a way, as the time taken to figure that out will place us well into rejuvenation therapy territory, achieved through means that have nothing to do with CR or CR mimetics.
joe_the_user 13y ago
I think you indirectly show how hard this kind of research is given that it be persuasively argued that the supposed "benefits" of "calorie restriction" are an artifact of studying mice and other animals who sit around doing nothing and/or are given a rather unhealthy died[1]. Indeed, we have some idea of the causes and cures for cancer. We don't know with much exactness the mechanisms of aging. [1] http://en.wikipedia.org/wiki/Calorie_restriction#Effects_of_CR_on_life_span_in_different_organisms http://en.wikipedia.org/wiki/Calorie_restriction#Effects_of_...
- exratione 13y ago
  There is a big difference between the mechanisms of aging (how exactly it unfolds) and the state of aging (a measure of the damage). The research community knows exactly what the fundamental differences between old tissue and young tissue are, because they have listed them all in the process of investigating the molecular pathology of age-related disease. What they argue over is how the differences happen, which differences are more important than others, and how metabolism reacts or contributes to the differences. That's all massively complex and poorly understood, but the damage isn't and is well understood. (For a layperson's list, see: http://sens.org/research/introduction-to-sens-research http://sens.org/research/introduction-to-sens-research ) The actual differences can be repaired or removed without resolving any of the outstanding questions as to what they do, what their mechanisms are, how they cause further pathology, where they came from. If you've removed all differences in tissue and not produced rejuvenation, then congratulations, you've proved that aging is a genetic/epigenetic program - and at a tiny cost compared to present investigations. But I think it's much more plausible that we'd see rejuvenation.
  - joe_the_user 13y ago
    There is a big difference between the mechanisms of aging (how exactly it unfolds) and the state of aging (a measure of the damage). The research community knows exactly what the fundamental differences between old tissue and young tissue are, because they have listed them all in the process of investigating the molecular pathology of age-related disease. I'm not sure exactly what you're point here is but if your point is we can get somewhere simply by directly manipulating the observed symptoms of age, I should point that while, of course, there are observable differences between old and new tissue, old and young organisms and so-forth, these differences aren't simply "symptoms of aging". Rather, observed differences are differences in the stable state reached between the continuous process of damage to parts and the continuous process of healing to parts. Changing X physiological state while changing nothing else is more or less as ridiculous moving hands around on a Swiss watch (not researcher don't try this - boo cholesterol drugs). Physiology of virtually any animal is very dynamic and still, still little understood.
ekianjo 13y ago
> and it would only take a decade and a billion dollars to demonstrate that in mice I thought Aubrey de Grey had already demonstrated that they were able to make long-lived mice in labs?
- exratione 13y ago
  No. You must be thinking of one of the many ways of extending life in mice through germline genetic alteration or other non-SENS-like methods. As to where the SENS Research Foundation is, you can look at their annual reports - it's all still foundation work on the necessary technologies at this point, and $4M/yr is nowhere near enough funding for optimal progress: http://sens.org/about/organizational-reports http://sens.org/about/organizational-reports
pasbesoin 13y ago
There is a very large, addressable, and under-appreciated factor is delayed aging: Stress reduction. Study after study, as well as pervasive anecdotal observation, demonstrate the role of stress in aging and deterioration. Unfortunately, reducing it for someone often means getting someone else to give something up (wealth, convenience, exploitative predilections, etc.). And so far, we've not been able to maintain such social cooperation where it has been established. Personally, a large factor in my life has been noise. I've had some incredibly inconsiderate neighbors as well as some rather ignorant and counter-productive employers. That's just one example -- anecdote. But studies continue to roll out documenting links between chronic stress and physical as well as mental deterioration. And "everyone" has observed a family member or friend rapidly look much older while and after going through a crisis. On a personal level, I'd recommend that people remove themselves from out-of-their-control stressful situations at the first opportunity.

Udo 13y ago

Can you point me to some research that indicates caloric restriction leading to a higher life expectancy in humans (compared to normal nutrition, not obesity of course)?

exratione 13y ago
Here's a starting point to summarize thoughts on that question from some of the better known researchers involved in human studies. http://impactaging.com/papers/v5/n7/full/100581.html http://impactaging.com/papers/v5/n7/full/100581.html "Whether or not CR will extend lifespan in humans is not yet known, but accumulating data indicate that moderate CR with adequate nutrition has a powerful protective effect against obesity, type 2 diabetes, inflammation, hypertension, cardiovascular disease and reduces metabolic risk factors associated with cancer." My summary of calorie restriction research is that it (a) produces similar-ish short term changes in metabolism and measures of health in mammals tried so far, and (b) is expected to have much smaller effects on life span in humans than in mice. The present consensus is that 5 years in humans would be on the high end, as I recall. The most interesting thing to resolve with certainty in this subfield is how the short-term measures can be so similar, how the expected reduction of age-related disease in humans can be so large, and yet the life expectancy outcome be so small. Should be interesting, in a post-facto sort of a way, as the time taken to figure that out will place us well into rejuvenation therapy territory, achieved through means that have nothing to do with CR or CR mimetics.

joe_the_user 13y ago

I think you indirectly show how hard this kind of research is given that it be persuasively argued that the supposed "benefits" of "calorie restriction" are an artifact of studying mice and other animals who sit around doing nothing and/or are given a rather unhealthy died[1]. Indeed, we have some idea of the causes and cures for cancer. We don't know with much exactness the mechanisms of aging. [1] http://en.wikipedia.org/wiki/Calorie_restriction#Effects_of_CR_on_life_span_in_different_organisms http://en.wikipedia.org/wiki/Calorie_restriction#Effects_of_...

exratione 13y ago
There is a big difference between the mechanisms of aging (how exactly it unfolds) and the state of aging (a measure of the damage). The research community knows exactly what the fundamental differences between old tissue and young tissue are, because they have listed them all in the process of investigating the molecular pathology of age-related disease. What they argue over is how the differences happen, which differences are more important than others, and how metabolism reacts or contributes to the differences. That's all massively complex and poorly understood, but the damage isn't and is well understood. (For a layperson's list, see: http://sens.org/research/introduction-to-sens-research http://sens.org/research/introduction-to-sens-research ) The actual differences can be repaired or removed without resolving any of the outstanding questions as to what they do, what their mechanisms are, how they cause further pathology, where they came from. If you've removed all differences in tissue and not produced rejuvenation, then congratulations, you've proved that aging is a genetic/epigenetic program - and at a tiny cost compared to present investigations. But I think it's much more plausible that we'd see rejuvenation.
- joe_the_user 13y ago
  There is a big difference between the mechanisms of aging (how exactly it unfolds) and the state of aging (a measure of the damage). The research community knows exactly what the fundamental differences between old tissue and young tissue are, because they have listed them all in the process of investigating the molecular pathology of age-related disease. I'm not sure exactly what you're point here is but if your point is we can get somewhere simply by directly manipulating the observed symptoms of age, I should point that while, of course, there are observable differences between old and new tissue, old and young organisms and so-forth, these differences aren't simply "symptoms of aging". Rather, observed differences are differences in the stable state reached between the continuous process of damage to parts and the continuous process of healing to parts. Changing X physiological state while changing nothing else is more or less as ridiculous moving hands around on a Swiss watch (not researcher don't try this - boo cholesterol drugs). Physiology of virtually any animal is very dynamic and still, still little understood.

ekianjo 13y ago

> and it would only take a decade and a billion dollars to demonstrate that in mice I thought Aubrey de Grey had already demonstrated that they were able to make long-lived mice in labs?

exratione 13y ago
No. You must be thinking of one of the many ways of extending life in mice through germline genetic alteration or other non-SENS-like methods. As to where the SENS Research Foundation is, you can look at their annual reports - it's all still foundation work on the necessary technologies at this point, and $4M/yr is nowhere near enough funding for optimal progress: http://sens.org/about/organizational-reports http://sens.org/about/organizational-reports

pasbesoin 13y ago

There is a very large, addressable, and under-appreciated factor is delayed aging: Stress reduction. Study after study, as well as pervasive anecdotal observation, demonstrate the role of stress in aging and deterioration. Unfortunately, reducing it for someone often means getting someone else to give something up (wealth, convenience, exploitative predilections, etc.). And so far, we've not been able to maintain such social cooperation where it has been established. Personally, a large factor in my life has been noise. I've had some incredibly inconsiderate neighbors as well as some rather ignorant and counter-productive employers. That's just one example -- anecdote. But studies continue to roll out documenting links between chronic stress and physical as well as mental deterioration. And "everyone" has observed a family member or friend rapidly look much older while and after going through a crisis. On a personal level, I'd recommend that people remove themselves from out-of-their-control stressful situations at the first opportunity.