At last, a sensible perspective on aging


The world is full of naive people who think we’re going to be immortal some day soon, in spite of all the evidence that says no (Kurzweil is a prominent example of such techno-optimism, as is Aubrey de Grey). It’s not just bad biology, it’s also bad physics, as Peter Hoffman explains. We’re all made of parts that are constantly being battered by thermal energy as an essential part of their operation, and damage accumulates until…we break down. This is unavoidable.

If this interpretation of the data is correct, then aging is a natural process that can be reduced to nanoscale thermal physics—and not a disease. Up until the 1950s the great strides made in increasing human life expectancy, were almost entirely due to the elimination of infectious diseases, a constant risk factor that is not particularly age dependent. As a result, life expectancy (median age at death) increased dramatically, but the maximum life span of humans did not change. An exponentially increasing risk eventually overwhelms any reduction in constant risk. Tinkering with constant risk is helpful, but only to a point: The constant risk is environmental (accidents, infectious disease), but much of the exponentially increasing risk is due to internal wear. Eliminating cancer or Alzheimer’s disease would improve lives, but it would not make us immortal, or even allow us to live significantly longer.

The article points out that we can accurately model mortality with only a few general parameters, and they’re rather fundamental and physics-dependent — we can tweak the biology as much as possible, but the underlying physical properties are going to be untouchable.

I would add, though, that while the mortality curves he shows are inevitable, biology can stretch and contract them, and we do have measurable variation in different species that shows that there is a kind of scaling factor to the curves in biological diversity — it’s not as if every species that lives at the same average temperature have identical life expectancies! Even within the human species, there are genetic variants that affect longevity, and clearly different life-style choices influence mortality, even though we’re every one of us ticking along at roughly the same 37°C. So please, yes, we can reduce the incidence of heart disease and cancer, and get a longer average lifespan…but even if we were to eradicate those major causes of mortality, we’re all going to get up around the century mark, and then we’re going to plummet off a cliff because of all the accumulated cellular damage and declining physiological efficiency.

By the way, one odd thing when I tried to find an illustration to accompany this post: I searched on “aging”. Almost all the photos on the web illustrate women by a huge margin. I am forced to conclude that only women suffer from the ravages of age; men simply get mature. But at least it’s one topic that women get to dominate!


  1. says

    Of course, evolution is propelled by the fate of organisms’ descendants. It’s not good to reproduce after we’ve been around long enough to acquire too many mutations, and by then we’re in the way anyhow. A limited lifespan is actually an adaptive advantage.

  2. says

    I disagree. It’s not an advantage. However, in a world where attrition is inevitable and imposes a limit on your lifespan, there is an advantage to living fast and hot and reproducing before you’re hit by a bus or eaten by a tiger or shit yourself to death with dysentery.

  3. prae says

    Sorry, but there is quite a huge leap from “thermal effects damage molecules” to “immortality will never ever be possible”. By that logic, shouldn’t procreation fail at some point, too?

    If you want to argue against absolute immortality, that part about the glass tubes (“death without aging”) is a way better example. But then, it should be obvious that after potential immortality is reached, the average life expectancy will just move to 300 or so, with the primary death cause being “random freak accident”

  4. says

    The way procreation succeeds is by extremely intense selection and pruning out of non-viable individuals. Procreation can fail billions of times in the effort to generate a survivor.

    We’ve been removing with greater and greater success the causes of early mortality. Notice that no one is living to be 300, or ever has.

  5. barbaz says

    I thought the main cause of aging is the shortening of telomeres. Okay, even without the telomere problem immortality might be out of reach because “forever” is a pretty long time, but wouldn’t it significantly increase our lifespan?

    Also, how do germ cells know to keep their telomeres intact, so that every generation does not die earlier than their parents?

  6. says

    Microorganisms often have circular loops of DNA. No telomeres.

    Telomeres don’t cause aging. Telomere shortening is trivial to counter — we’ve got telomerases that can extend them, but we don’t, at least not in somatic cells. Why not? Because all cells accumulate genetic damage with each replication event, and that’s the danger — telomere shortening is a clock cells use to estimate number of cell divisions that have occurred, as a signal to terminate a lineage before it is likely to be destructive to the organism as a whole.

  7. cmutter says

    Already we’re getting to where lots of people get hit with serious cognitive decline before dying of other causes. If we don’t defeat cognitive decline somehow, we’ll probably end up with a world where most deaths are voluntary. (Or lots of people living with no awareness of what’s going on around them).

  8. says

    Re: Accumulated damage.

    As I see it it’s theoretically possible as long as one can keep a master record. We kinda have that in the form of adult stem cells, but only to a limited degree. As they are exposed to the same damage as the rest of the cells it’s only a matter of time before they also succumb to this wear.

    So in theory we could keep a fresh supply of stem cells in a lab, checked for mutations. But even then the body isn’t designed for perpetual life, so the tools needed for eliminating all mutations isn’t there. And I don’t see how we could add these without re-engineering the genome from scratch.

  9. says

    How do you keep a “fresh” supply of stem cells in a lab? How do you check them for mutations? The conditions for in vitro viability are almost certainly antithetical to in vivo maintenance of a multicellular organism.

    Right now we keep a fresh supply of stem cells in our bodies for replacement and repair. They get depleted. They accumulate errors, too.

  10. says

    It has always seemed to me that “ageing” is a ln accumulation of failures of various systems, each of which fails uniquely and at its own rate. So there is no single fix that can be applied – we’ll need an immortality for brains, another immortality for joint cartilage, another immortality for skin, and so forth. Fractally detailed immortalities for those subsystems that consist of sub-subsystems (e.g: kidneys)

    It seems analogous to the car collector who wants to make an immortal car and manufactures an engine with ceramic heads and bearings. That gives them a nearly immortal engine until the piston rings fail. And when they sort out the engine, the transmission falls out before they even get to notice the chassis is rusting.

    We are not made of systems thay fail at the same speed yet they are very interdependent. I realized this a while ago when an acquaintance’s relative had a massive stroke that wiped out his brain but he had a pacemaker that kept his heart cheerfully beating away for days.

  11. says

    “…men simply get mature.”
    I’m 69 (which sounds so much better in French) and anyone who knows me can vouch that this is not necessarily true.

  12. prae says

    @Master record/Fresh stem cells: I think printing DNA molecules from digital storage isn’t that unrealistic. I’m almost certain it has actually been done already, albeit “only” for bacteria. Problems to still be solved would be things like long-term stem cell storage (possibly by freezing) and replacing the dna in the cell’s nuclei without damaging either the cell or the dna.

    The important question is: do stem cells replace lost neurons? I think THAT is the most important question if one wants to live potentially forever. Also, at which rate can neurons be replaced, if at all, so that you still keep your memories and everything else which makes you “you”?

  13. jerthebarbarian says

    Pfft – biological immortality. There’s no way to save the meatsacks – that’s why the only true immortality is to upload our brains into computers. Only then will we truly be able to live forever!

    (Is it just me, or does the drive for immortality very much feel more like a religious proposition than a scientific one?)

  14. Elladan says

    I’m sure there are a lot of amusing sci-fi ways to imagine fixing the problems of aging, stem cells, neurons, etc. I mean, how about better error correcting operation in our cellular machinery? Extra parity information in DNA! Whee!

    The problem with all that is that it’s not something that will happen any time soon. Sure maybe in a few centuries or something things will be different… But people like Ray Kurzweil are talking about it in a decade. That’s less time than it takes to make a new airplane or major software product!

    Their delusion isn’t based on making a few tweaks to existing technology: they’re assuming we’ll invent AI gods who will do thousands of years of work for us in an eyeblink. It’s absolutely like religion.

  15. johnhodges says

    Decades ago I read a book (title and author recalled only vaguely) that made this argument: Species develop “typical” lifespans as an adaptation to their risk of being killed. A species can put metabolic effort and resources into repair and maintenance, or (alternatively) into reproduction and childcare. Species that suffer high rates of predation live short, vigorous lifespans and have large litters(e.g. mice); species that have good defenses against predation live long, sedate lifespans (e.g. elephants and tortoises) and breed slowly.

    Calorie restriction has lengthened the lifespans of every experimental animal on which it has been imposed, by 30 to 50 percent; this is consistent with the theory that when times are consistently lean, the body figures (figuratively) that this is not a good time to try to reproduce, so it switches more effort toward repair and maintenance in the hope of surviving until times are better.

  16. says

    In today’s NYT, a long form story on research into slowing the aging process. Quoth:

    Most of us harbor the intuition that we age because our bodies, like our cars, our furniture, our patience, just wear out. But the best argument that life span is not hard-wired, biologists say, has long been evident: Living things age at significantly different rates.

    “The squirrels in my neighborhood have a 25-year life span, but they look like rats that live two years,” said Gary Ruvkun, a pioneer in aging biology at Harvard Medical School. “If you look at what nature has selected for and allowed, it suggests that you might be able to get your hands on the various levers that change things.”
    Continue reading the main story

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    That aspiration gained traction in the 1990s and 2000s, when scientists, armed with new tools of molecular biology, homed in on the complex cellular pathways that regulate life span in many species. By removing genes that produced certain proteins, or adding genes that produced others, researchers found they could significantly extend the lives of simple laboratory organisms like budding yeast, roundworms and flies.

    “It’s not just wearing out, it’s a program,” Dr. Ruvkun said. “The genetics told us that. If you can modulate it with a few simple perturbations, that’s the definition of a program.”

    Not saying I’m for it or against it, just sayin’ it isn’t pseudoscience.

  17. numerobis says

    only women suffer from the ravages of age; men simply get mature

    Women suffer the ravages of age, men simply die.

    My grandfather was very popular among the ladies in his senior community, particularly after grandmother passed away. A 94-year-old single man is quite a catch!

  18. brett says

    There are mammals that live significantly longer than a century, like those 200-year-old Bowhead Whales. It seems to be tied into resistance to cancer, like how naked mole rats have surprisingly long life spans for rodents.

    Of course, that’s not the same thing as immortality. But it’s something to look into – if we could greatly increase human resilience to the damage that leads to cancer, then we might be able to push life-spans further out.

  19. slithey tove (twas brillig (stevem)) says

    only women suffer from the ravages of age; men simply get mature

    Women suffer the ravages of age, men simply die.

    That’s always been my impression also. We (the Intertubez) is always bombarded with “This is the oldest living person in the world”, and always it is a woman. When about an aged man, the title always includes the qualifier, man; as his age always is less than the oldest person (who happens to be a woman).

    I’ve always wondered if there is a genetic component to providing females with longer lifespans than the males; from the role they play nurturing their grandchildren. The males just burn out from overwork, and are “designed” [passive tense] for speed. age makes them slow down, so genes let them die younger than females.

    oops looks like I slipped into the trap of assuming, “there’s a gene for everything about human health/disease/mortality”.
    but in defense, I just like to play around with these traps, for fun.

  20. Nerd of Redhead, Dances OM Trolls says

    brett #18

    like how naked mole rats have surprisingly long life spans for rodents.

    The reason for the cancer resistance in naked mole rats is known.

    The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years1, 2, 3. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years4, 5. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer2, 6. Here we identify a mechanism responsible for the naked mole rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

    Or, it may be a side effect of the need for the more elastic skin.

  21. jim959 says

    Modern medicine has increased the average lifespan, making the average lifespan closer to the maximum. There is no physics based reason to think the maximum lifespan is fixed. Maximum lifespan differs, often considerably, for organisms of similar size and lifestyle. There is a lot of evidence that maximum lifespan is a feature that can easily be changed by evolutionary pressure. There are also many genes known in model organisms to increase maximum lifespan when mutated or present in extra copies.

    While we can’t change maximum human lifespan now, if we gain a better understanding of the processes in the cell that set the lifespan it may be possible to find drugs that alter maximum lifespan. That said, you can be optimistic we’ll make progress on this quickly or pessimistic…

  22. unclefrogy says

    well I would agree that the idea of immortality being achieved is a religious idea. I would suggest that it is even primarily a western idea (if you include egypt). The idea of a personal soul or personal existence after death something separate from our bodily existence is mostly western in that sense.
    This idea of uploading to a computer of ourselves how is that not moving our “soul” to a more easily repaired body which would be at least for the early adopters a simulated living body which is mostly dead already.
    Even if all the problems are solved and we even have the choice of a real meat body or a completely manufactured synthetic one and we can continue on indefinitely from what we can tell the universe will not continue in any way similar to the state it is at the “present”. Our local star will eventually exhaust itself as will all of the others which will be spread out at even more impossible distances as expansion continues. Does anyone seriously think that we can somehow survive what ever the ultimate fate of the universe will be ?
    immortality as “preached” is indeed a religious idea.
    like the idea that we were “created by aliens” does not solve anything it just adds an other question of where did the aliens come from?
    it is turtles all the way down makes as much sense,
    it seems to me that the focus is in the wrong direction one that leads the long way to no where.
    uncle frogy

  23. says

    @PZ #9: Non-destructive DNA-testing is probably a stretch, but as #12 prae suggested a digital record might be doable.
    It’s not anywhere near enough to achieve immortality, but it could in theory increase lifespan significantly. It’s not like this place is getting over-populated or anything, so why not?

  24. unclefrogy says

    well the advantage to a digital existence is computers do not need to eat food and eliminate waste and can be extremely small but they do require energy and maintenance. which would give the less fortunate jobs !
    uncle frogy

  25. says

    @ 24: I wasn’t suggesting a digital existence, just the possibility of a manufactured genome from a digital copy. That would provide an endless supply of pristine stem cells.

  26. DanDare says

    Go cyborg. Replaceable parts. The brain then becomes the big problem. Brain in a box probably gets us as close as possible to our maximum life span.
    As for me I have a daughter my core memes have already jumped ship .

  27. dannysichel says

    if you assume that memory has a physical substrate, then there can be no personal immortality, because eventually you’ll run out of matter in which to store your memories.

    Oh, it might take billions of years… trillions… quadrillions… quintillions… but that’s the thing about “immortality”. It’s not “not die for a long long long time”. It’s “not die, ever“. And once your memory substrate is saturated, you can either start forgetting old things (the first step in replacing your selfness, which is counter to the whole idea of personal immortality in the first place), or stop ever remembering new things (in which case, how can you really know you’re alive).

  28. sonderval says

    I do not understand how a thermodynamic model (where life expectancy should be related to body temperature) can be reconciled with the known scaling relation that states that for mammals, life expectancy is roughly determined by the number of heartbeats (i.e., it is inversely proportional to the metabolic rate).
    And I would like to see at least an order-of-magnitude estimate of how thermodynamics would determine the life span to be of the order of years, not minutes or centuries.
    Since you are usually very wary of simple physics models to explain biology, why not here?

  29. prae says

    @27 dannysichel: Having a life expectancy of billions of years should be more than enough to figure out something better in order to store your memory. A very long-living scientist could use this time to figure out how the brain actually works in order to reorganize it for a potentially endless existence.

    @23 unclefrogy: Oh, you would still have a metabolism in digital form, in a sense. A) you would require energy, as you said, and B) you would need replacement parts. Even if you live off solar energy without burning anything, you would effectively still need to consume iron, silicon, copper, etc, and excrete electronic waste.

    And then, there is another thing about immortality/extreme longlevity: While I would like it for myself, I think it would do enormous damage to human society. I mean, imagine those people who used to discriminate against left-handed people would be still alive. I think most of the changes in today’s society are only possible because the old douchebags holding on to the old values are dying off.

  30. Dunc says

    If you’re going to go for true immortality – as in forever – then things are going to start getting pretty dull after the heat death of the Universe.

  31. rietpluim says

    Though I don’t feel like dying, I don’t think I’d want to live forever either.

  32. says

    There are many good reasons to criticize Kurzweil, de Grey, etc, but the second law of thermodynamics isn’t one of them. Yes, it states that the entropy of an isolated system must always increase, but a living organism isn’t isolated. The human body maintains internal order by consuming substances with low entropy and excreting substances with high entropy. There is no fundamental physical reason why this can’t continue so long as the necessary consumables are available.

  33. Rob Grigjanis says

    hyperdeath @32: From the paper I linked @33:

    It has been suggested that any entropy increase in an organism can always be counteracted without repercussions by simply expending energy; from this, some have concluded that there is no thermodynamic stipulation for aging to occur and no role for thermodynamics in explaining aging. This is a rather obvious non sequitur—yet this notion has been perpetuated in the aging literature, both explicitly and implicitly (Kirkwood, 1999; Mitteldorf, 2010; Trindade et al., 2013). It will be demonstrated here why this inference is a logical fallacy and how it neglects to consider the effects of internal entropy production
    within an organism—particularly the influence of internal entropy production on the flow of biomolecular-encoded information over time.

  34. sonderval says

    Thanks for the link, it seems that this idea is much better researched than I expected it to be.

  35. Nick Gotts says

    Notice that no one is living to be 300, or ever has. – PZM

    True, but a hell of a lot more people are living to 100. In the last half century, by far the biggest absolute decreases* in death rates in rich countries has been in the over-70s. See here for UK 1963/2013 figures.

    And notice that the very article you link to ends thus:

    That doesn’t mean there is nothing we can do. More research into specific molecular changes in aging is needed. This may show us if there are key molecular components that are the first to break down, and whether that breakdown leads to the subsequent cascade of failure. If there are such key components, we would have clear targets for interventions and repair, possibly through nanotechnology, stem cell research, or gene editing. It’s worth a try. But we need to be clear about one thing: We’ll never defeat the laws of physics.

    *By “absolute decreases in death rates” I mean the percentage dying per year at the earlier date minus the percentage dying per year at the later.

  36. Nick Gotts says

    Already we’re getting to where lots of people get hit with serious cognitive decline before dying of other causes. – cmutter

    Actually, recent European data shows that the increase in dementia has been considerably slower than expected, given the aging of the population. This is a poorly-written article, but AFAIK the figures are right. Improved cardiovascular health due to both lifestyle changes and better treatments is thought to be the main factor.

    Calorie restriction has lengthened the lifespans of every experimental animal on which it has been imposed, by 30 to 50 percent – johnhodges@15

    This is at least doubtful with respect to rhesus monkeys – which are clearly more relevant to humans than nematodes, fruit flies, or even rats. If we take both experimental studies reported as valid, it looks to me as though eating 30% less calories than they would if allowed to eat as much as they wanted was beneficial, but there was a point well short of starvation where further reductions produced no benefit. I’d guess monkeys allowed to eat as much as they wanted probably got pretty chubby. I know I would if I ate as much as I wanted!

  37. emergence says

    Is around a century give or take a decade or two really as long as any animal can live? Even if we can’t live forever, or even for thousands of years, could we at least double our current lifespan? What research has been done on the absolute, physics-enforced upper limit on an individual animal’s maximum lifespan?