Human age limit claim sparks debate | Hacker News Reader

Human age limit claim sparks debate

nature.com

38 pointsothello30 comments

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.

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?

https://en.wikipedia.org/wiki/CRISPR#Cas9

Sorry, I fail to see the connection?

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.

Working out regularly would certainly make your "health state" better than average.

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.

The effects of aging aren't recognized as a disease. I'm all for changing that and treating aging as a disease. That's the distinction I'm making. Barring diseases and injuries, the human lifespan hasn't been extended. The average lifespan has been extended because we can treat diseases and injuries -- that is wonderful. The lifespan of a healthy person -- how long a disease- and injury-free person can live -- hasn't changed, and that's medicine's blind spot I was talking about.

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.

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.

> telomeres always shorten with each mitosis

mmmh not always, there are at least one exception.

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

Exact

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

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.

This is not how the body operates, skin and gut cells reproduce far more often than normal.

According to the paper I linked to, as of 2014 that was a long-held assumption, one that has lead to a number of "paradoxes" (ie, is in conflict with observation). What evidence are you thinking of?

The most obvious is the response to heavy radiation poising or chemotherapy show a range of responses consistent with various rates of cell division.

Thanks, can you link to a paper you are thinking of? Actually I think right now we are totally talking past each other.

I think the confusion is due to you thinking of the total number of cell divisions, while I am thinking of the number of divisions separating a given cell from the zygote.

This lead me to misunderstand the relationship you were claiming between "This is not how the body operates" and "skin and gut cells reproduce far more often than normal".

I think we where talking past each other.

Bone marrow for example needs to continuously create Blood cells with a short lifespan. (Adult humans have roughly 20–30 × 1012 (20–30 trillion) red blood cells at any given time, comprising approximately 70% of the total human body cell number.) https://en.m.wikipedia.org/wiki/Red_blood_cell

Thus your bone marrow must create new cells at a much faster rate than average, making the average a meaningless number.

Now you might think you could design bone marrow to minimize the number of generations nessisary to produce that blood, but it does not operate with such efficiency. In large part because fewer cell generations does not mean fewer mutations.

If you check the paper, you will see it describes a scheme that minimizes the number of generations while maintaining the observed rate of cell division. The average rate of division across tissues isn't really at issue here, tissues that require fewer cells will just have a shallow hierarchy.

>"it does not operate with such efficiency"

Most likely it does not operate at max efficiency. However, since most mutations seem to occur during mitosis, it would make a lot of sense for natural selection to optimize (number of divisions)/(generations from zygote).

First, it's not the number of generations that are the direct risk. A cell that does nothing will still mutate over time. It's large numbers cells that share a few risky mutations that are the problem.

If you have a 1,000 cells that can do 30 generations without hitting programmed cell death then a single mutation that kicks that off can form a large mass without tripping your body's alarms which also share that mutation. Even if they end up as a non cancerous mass that large mass is very likely to cause problems.

On the other hand if you have 1 billion cells that can each do 10 generations and they all formed young you still get the same 1 trillion cell potential, but don't risk that single mutation as those 1 Billion cells showed up at a young age. Further, when some of those 1 million cells start growing uncontrollably they only grow to 1,000 cells before hitting programmed cell death which is a lower cancer risk.

Now sure, the body can play around with these numbers to form a crazy number of skin, gut, and blood cells from some relatively small cell pools. But, it's already playing those games while minimizing cancer risk. So, we don't have some pool of 'young' cells to solve problems late in life because it's to dangerous to keep them around.

PS: People often thing of their body's as kind of a tub of undifferentiated mass. But, cells a body structures are optimized for a huge number of problems that only become obvious with deep investigation.

>"First, it's not the number of generations that are the direct risk. A cell that does nothing will still mutate over time. It's large numbers cells that share a few risky mutations that are the problem."

If this is correct, I think you would likely be right. Do you have a reference?

What about: https://en.wikipedia.org/wiki/Gompertz%E2%80%93Makeham_law_o...

The people who live to be 120, etc are already stragglers. Also, there are a huge variety of statistical distributions with fatter/thinner tails, so "not statistically distributed" isn't a real thing...

If you download some mortality data, start exploring it, and looking up previous work you will quickly learn all of the above. Try it out: http://www.nber.org/data/vital-statistics-mortality-data-mul...

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

[2]: http://dailybruin.com/2010/03/04/autopsy-115-year-old-aids-r...

[3]: http://www.uclb.com/news-and-events/news-post/potential-new-...

[4]: http://www.sens.org/research/introduction-to-sens-research

[5]: http://dx.doi.org/10.1159/000357670

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

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.

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.

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

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.

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