7 ms·

Human age limit claim sparks debate

38 points by othello 10y ago

reasonattlm 10y ago
It serves as a reminder that the research community actually knows very little about the demographics of aging at very advanced age. The data is so sparse past age 110 that the statistics of mortality, very reliable in earlier old age, rapidly turn into a sludge of uncertainty. It is possible at this point in time to argue either side of the position that there is or is not a limit to longevity under present circumstances, though most of us probably think that one or the other side is weak. On the one hand we can theorize that maximum human life span is increasing, in a way analogous to the fact that life expectancy at 60 is inching upward at a year every decade, but more slowly, and we might suggest the data for extreme old age is so bad that the ongoing change can't be identified. On the other hand we can instead theorize that there is some limiting process that hasn't changed at all over the course of recent human history, is not impacted meaningfully by modern medicine, plays a very large role in supercentenarians in comparison to younger old people, and renders mortality rates so very high at the extremes of human life spans as to form a limit. This is actually a point worth making twice: when limits to lifespan are discussed, we're not talking about actual limits per se, but effective limits. A very large mortality rate, possibly coupled with rapid growth in mortality rate over time, looks a lot like a hard barrier to further progress in practice, but there is still the chance that someone could beat the odds. Where the data for supercentenarians is good enough to fill in tentative mortality rates with large error bars, up to age 115, that rate is around 50% annually [1]. The mortality rate may increase greatly after that point, and that would be entirely expected given the absence of more than the one certified example making it past 120, but it is very unclear from the limited data. Mortality rates reflect actual physical processes, the accumulation of forms of cell and tissue damage that cause the suffering, death, and disease of old age. The damage is the same, but the proximate causes of death for supercentenarians are quite differently distributed from those of younger old people, prior to a century of age. The majority appear to be killed by transthyretin amyloidosis [2] that clogs up the cardiovascular system, and that is becoming known to play a much lesser - but still significant role - in heart disease in earlier old age. Could this form of amyloidosis be the candidate for a process that is not all that affected by the past century of changes in medicine and lifestyle, and that becomes much more important in extreme old age than early old age? Possibly. The only way to know for sure is to build ways to clear this form of amyloid [3] and see what happens. The natural state of aging is a function of damage and how medicine addresses that damage - which is poorly and next to not at all at the present time. Almost all medicine for age-related conditions fails to address their root causes, the cell and tissue damage of aging [4], and takes the form of patching over that damage in some way or coaxing biological machinery to cope slightly better with running in a damaged environment. Predictably it is expensive and only marginally effective in comparison to true repair. As above in the comments on amyloidosis, find a way to repair that problem and life span will increase, as the machinery of biology will be less damaged and less worn down into high rates of failure. That is the point to take away from this discussion. It has to be said that the lead of the study, Jan Vijg, comes across as very pessimistic on aging in his comments here when considered in comparison to past remarks and collaborations with SENS folk [5] that I've seen from him. That is the case even granting that he is in the camp of researchers who believe there is no alternative to a very slow and expensive reengineering of human metabolism in order make incremental gains in life span and slowing of the aging process. [1]: http://dx.doi.org/10.1007/978-3-642-11520-2 http://dx.doi.org/10.1007/978-3-642-11520-2 [2]: http://dailybruin.com/2010/03/04/autopsy-115-year-old-aids-research/ http://dailybruin.com/2010/03/04/autopsy-115-year-old-aids-r... [3]: http://www.uclb.com/news-and-events/news-post/potential-new-approach-to-the-treatment-of-systemic-amyloidosis http://www.uclb.com/news-and-events/news-post/potential-new-... [4]: http://www.sens.org/research/introduction-to-sens-research http://www.sens.org/research/introduction-to-sens-research [5]: http://dx.doi.org/10.1159/000357670 http://dx.doi.org/10.1159/000357670
- madebysquares 10y ago
  One of the best most thorough comments I've ever seen. Thank you for citing all those sources.
tracker1 10y ago
It looks like not many people died in the 70's, I think we need to bring back disco, bell bottoms and pot smoking! Seriously though... antibiotics and widely available and distributed vaccinations have done more for human longevity on average than anything else.
- oldmanjay 10y ago
  Disco-descendants and weed are perennially popular and I'm sure bell bottoms will come back through the endless cycle of fashion repetition. Devise some experiments now to test your hypothesis.
bsder 10y ago
The big issue is that mortality seems to not fit any of the normal statistical distribution models. If it did, we would have a few stragglers at 150+ years old. That never happens. So, the question becomes: "What is inherent in the human body that causes mortality to not be statistically distributed?" That's the real argument.
- samatman 10y ago
  We know of at least one such thing: telomeres. Cells have a definite amount of time before they undergo mitosis, and telomeres always shorten with each mitosis. This puts at least one limit on longevity; there are likely to be others. Evolution exerts little-to-no selection pressure for organisms to survive past the caretaker period; in humans, that's grandparents at most.
  - pvaldes 10y ago
    > telomeres always shorten with each mitosis mmmh not always, there are at least one exception.
    - brainfire 10y ago
      Specifically, the HeLa line (human cancer-derived) is an exception (not sure if it's what you were referring to): https://en.wikipedia.org/wiki/HeLa https://en.wikipedia.org/wiki/HeLa
      - pvaldes 10y ago
        Exact
  - nonbel 10y ago
    Not necessarily an issue: "Approximately 7x10^15 mature cells are produced in a human lifetime and these could be produced in 53 cell generations (2^53 = 9x10^15). In 60 cell generations a total of 10^18 cells would be produced, enough for over 1000 years of human life. Thus it is possible that, even in extreme old age, the mature cells of the body are fewer than 60 generations from the zygote." https://www.ncbi.nlm.nih.gov/pubmed/25459141 https://www.ncbi.nlm.nih.gov/pubmed/25459141 It may be that rather than limiting lifespan, telomere length is a result of other constraints on lifespan. There may be no point to making them longer.
zargon 10y ago
Medicine hasn't even attempted to extend human lifespan. To date it has only adressed causes of premature death. These conclusions have this baked-in as a (quite probably unconscious) assumption. Medicine needs to grow beyond this short-sightedness.
- Iv 10y ago
  Also, medicine is only concerned about bringing people with problems back to the "average normal" health state. What if I want to improve on the average?
  - toomuchtodo 10y ago
    https://en.wikipedia.org/wiki/CRISPR#Cas9 https://en.wikipedia.org/wiki/CRISPR#Cas9
    - Iv 10y ago
      Sorry, I fail to see the connection?
      - toomuchtodo 10y ago
        CRISPR allows for the in place editing of your genome, which is going to be necessary to extend your life significantly or make you an above average human.
  - danielhooper 10y ago
    Working out regularly would certainly make your "health state" better than average.
- danielhooper 10y ago
  This will just turn into a silly argument over semantics. It's not as if a natural death is just suddenly passing from old age. You succumb to some kind of disease that destroys a critical part of your body. Modern medicine does a lot when it comes to preventing and curing diseases, so I'm not sure where your argument that medicine hasn't attempted to extend our lives comes from.
astaroth360 10y ago
Yeah, except they don't include any sort of scientific advance. Who cares about the natural age limit? We're mankind, the first species to be able to guide our own evolution. Basically this article means nothing significant.
vorotato 10y ago
I read the title and thought they were talking about a legal limit. Sir you are 15 years older than the legal limit.

38 points by othello 10y ago

It serves as a reminder that the research community actually knows very little about the demographics of aging at very advanced age. The data is so sparse past age 110 that the statistics of mortality, very reliable in earlier old age, rapidly turn into a sludge of uncertainty. It is possible at this point in time to argue either side of the position that there is or is not a limit to longevity under present circumstances, though most of us probably think that one or the other side is weak. On the one hand we can theorize that maximum human life span is increasing, in a way analogous to the fact that life expectancy at 60 is inching upward at a year every decade, but more slowly, and we might suggest the data for extreme old age is so bad that the ongoing change can't be identified. On the other hand we can instead theorize that there is some limiting process that hasn't changed at all over the course of recent human history, is not impacted meaningfully by modern medicine, plays a very large role in supercentenarians in comparison to younger old people, and renders mortality rates so very high at the extremes of human life spans as to form a limit. This is actually a point worth making twice: when limits to lifespan are discussed, we're not talking about actual limits per se, but effective limits. A very large mortality rate, possibly coupled with rapid growth in mortality rate over time, looks a lot like a hard barrier to further progress in practice, but there is still the chance that someone could beat the odds. Where the data for supercentenarians is good enough to fill in tentative mortality rates with large error bars, up to age 115, that rate is around 50% annually [1]. The mortality rate may increase greatly after that point, and that would be entirely expected given the absence of more than the one certified example making it past 120, but it is very unclear from the limited data. Mortality rates reflect actual physical processes, the accumulation of forms of cell and tissue damage that cause the suffering, death, and disease of old age. The damage is the same, but the proximate causes of death for supercentenarians are quite differently distributed from those of younger old people, prior to a century of age. The majority appear to be killed by transthyretin amyloidosis [2] that clogs up the cardiovascular system, and that is becoming known to play a much lesser - but still significant role - in heart disease in earlier old age. Could this form of amyloidosis be the candidate for a process that is not all that affected by the past century of changes in medicine and lifestyle, and that becomes much more important in extreme old age than early old age? Possibly. The only way to know for sure is to build ways to clear this form of amyloid [3] and see what happens. The natural state of aging is a function of damage and how medicine addresses that damage - which is poorly and next to not at all at the present time. Almost all medicine for age-related conditions fails to address their root causes, the cell and tissue damage of aging [4], and takes the form of patching over that damage in some way or coaxing biological machinery to cope slightly better with running in a damaged environment. Predictably it is expensive and only marginally effective in comparison to true repair. As above in the comments on amyloidosis, find a way to repair that problem and life span will increase, as the machinery of biology will be less damaged and less worn down into high rates of failure. That is the point to take away from this discussion. It has to be said that the lead of the study, Jan Vijg, comes across as very pessimistic on aging in his comments here when considered in comparison to past remarks and collaborations with SENS folk [5] that I've seen from him. That is the case even granting that he is in the camp of researchers who believe there is no alternative to a very slow and expensive reengineering of human metabolism in order make incremental gains in life span and slowing of the aging process. [1]: http://dx.doi.org/10.1007/978-3-642-11520-2 http://dx.doi.org/10.1007/978-3-642-11520-2 [2]: http://dailybruin.com/2010/03/04/autopsy-115-year-old-aids-research/ http://dailybruin.com/2010/03/04/autopsy-115-year-old-aids-r... [3]: http://www.uclb.com/news-and-events/news-post/potential-new-approach-to-the-treatment-of-systemic-amyloidosis http://www.uclb.com/news-and-events/news-post/potential-new-... [4]: http://www.sens.org/research/introduction-to-sens-research http://www.sens.org/research/introduction-to-sens-research [5]: http://dx.doi.org/10.1159/000357670 http://dx.doi.org/10.1159/000357670

madebysquares 10y ago
One of the best most thorough comments I've ever seen. Thank you for citing all those sources.

tracker1 10y ago

It looks like not many people died in the 70's, I think we need to bring back disco, bell bottoms and pot smoking! Seriously though... antibiotics and widely available and distributed vaccinations have done more for human longevity on average than anything else.

oldmanjay 10y ago
Disco-descendants and weed are perennially popular and I'm sure bell bottoms will come back through the endless cycle of fashion repetition. Devise some experiments now to test your hypothesis.

bsder 10y ago

The big issue is that mortality seems to not fit any of the normal statistical distribution models. If it did, we would have a few stragglers at 150+ years old. That never happens. So, the question becomes: "What is inherent in the human body that causes mortality to not be statistically distributed?" That's the real argument.

samatman 10y ago
We know of at least one such thing: telomeres. Cells have a definite amount of time before they undergo mitosis, and telomeres always shorten with each mitosis. This puts at least one limit on longevity; there are likely to be others. Evolution exerts little-to-no selection pressure for organisms to survive past the caretaker period; in humans, that's grandparents at most.
- pvaldes 10y ago
  > telomeres always shorten with each mitosis mmmh not always, there are at least one exception.
  - brainfire 10y ago
    Specifically, the HeLa line (human cancer-derived) is an exception (not sure if it's what you were referring to): https://en.wikipedia.org/wiki/HeLa https://en.wikipedia.org/wiki/HeLa
    - pvaldes 10y ago
      Exact
- nonbel 10y ago
  Not necessarily an issue: "Approximately 7x10^15 mature cells are produced in a human lifetime and these could be produced in 53 cell generations (2^53 = 9x10^15). In 60 cell generations a total of 10^18 cells would be produced, enough for over 1000 years of human life. Thus it is possible that, even in extreme old age, the mature cells of the body are fewer than 60 generations from the zygote." https://www.ncbi.nlm.nih.gov/pubmed/25459141 https://www.ncbi.nlm.nih.gov/pubmed/25459141 It may be that rather than limiting lifespan, telomere length is a result of other constraints on lifespan. There may be no point to making them longer.

zargon 10y ago

Medicine hasn't even attempted to extend human lifespan. To date it has only adressed causes of premature death. These conclusions have this baked-in as a (quite probably unconscious) assumption. Medicine needs to grow beyond this short-sightedness.

Iv 10y ago
Also, medicine is only concerned about bringing people with problems back to the "average normal" health state. What if I want to improve on the average?
- toomuchtodo 10y ago
  https://en.wikipedia.org/wiki/CRISPR#Cas9 https://en.wikipedia.org/wiki/CRISPR#Cas9
  - Iv 10y ago
    Sorry, I fail to see the connection?
    - toomuchtodo 10y ago
      CRISPR allows for the in place editing of your genome, which is going to be necessary to extend your life significantly or make you an above average human.
- danielhooper 10y ago
  Working out regularly would certainly make your "health state" better than average.
danielhooper 10y ago
This will just turn into a silly argument over semantics. It's not as if a natural death is just suddenly passing from old age. You succumb to some kind of disease that destroys a critical part of your body. Modern medicine does a lot when it comes to preventing and curing diseases, so I'm not sure where your argument that medicine hasn't attempted to extend our lives comes from.

astaroth360 10y ago

Yeah, except they don't include any sort of scientific advance. Who cares about the natural age limit? We're mankind, the first species to be able to guide our own evolution. Basically this article means nothing significant.

vorotato 10y ago

I read the title and thought they were talking about a legal limit. Sir you are 15 years older than the legal limit.