Make Room! Make Room!

There is a recent article in Phys Rev Letters (“Programed Death is Favored by Natural Selection in Spatial Systems”) arguing that aging is an adaptation – natural selection has favored mechanisms that get rid of useless old farts.  I can think of other people that have  argued for this – some pretty smart cookies (August Weismann, for example, although he later abandoned the idea) and at the other end of the spectrum utter loons like Martin Blaser.

If this were the case, it would be a good thing, because we could then hope to significantly extend the human lifespan just by interfering with key steps in the programmed aging mechanism.

We would be able to easily identify those key steps because of natural experiments – people born with mutations that screwed up their kill switch and therefore lived lots longer than normal – you know, like those inventions that get released by mistake (the gasoline pill, the 100 mpg carburetor, etc.) .  The problem is, I  have never heard of any such slow-aging genetic syndrome. I don’t think any exist in humans. Too bad.  And humans are the species to look at – not just because we hope to apply this to humans, but also because we know an enormous amount about human genetics.  Milo of Crotona couldn’t lift a current paper edition of OMIM .

On the other hand, there may well be cases in which something like this happens in other species, particularly in semelparous organisms – those that reproduce only once, like Pacific salmon. Normally those salmon go back to their original spawning grounds, breed and die. In dying, they create a nutrient-rich environment for their off spring, and for other offspring that are on average closely related.  You can see how programmed death might pay off in this case. A simple change does slow down senescence in those salmon: castration before they flame out triples their life span.

There might could be mutations that significantly extended lifespan but had consequences that were bad for fitness, at least in past environments –  but that isn’t too likely if mutational accumulation and antagonistic pleiotropy are the key drivers of senescence in humans. As I said, we’ve never seen any.

It is possible that old people were once useful (materially contributed to the fitness of near relatives), especially in preliterate days.  Back in the ice age climate could change rapidly (Dansgaard-Oeschger  cycles) – old farts may have remembered previous climates, and that might have been useful.  When Peter Panum studied the 1846 measles epidemic in the Faeroes, he found that quarantine could prevent contagion – but  the old farts that had lived through the 1781 epidemic already knew that. People who listened to them, about a quarter of the population, were shielded from the epidemic.

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65 Responses to Make Room! Make Room!

  1. Fourth doorman of the apocalypse says:

    When Peter Panum studied the 1846 measles epidemic in the Faeroes, he found that quarantine could prevent contagion – but the old farts that had lived through the 1781 epidemic already knew that. People who listened to them, about a quarter of the population, were shielded from the epidemic.

    Wouldn’t this knowledge become less and less useful in the face of repeated epidemics, because the population would come to contain more and more individuals with natural immunity?

    (Because genes for susceptibility would be removed from the population over time?)

  2. RCB says:

    I can’t help but be annoyed (maybe irrationally) by the reliance on physical terminology (is “mean-field theory” really necessary here, or is it just a way of signaling that you come from a high prestige field?), and sentences like “The mechanism is fundamentally different from those underlying standard evolutionary theories.” One gets the idea that it never occurred to geneticists and ecologists that population structure are key drivers of selection pressures. That all population genetics models assume panmixia. Come on now.

    Still, the result is interesting. They say that long-range dispersal kills this result. Exactly how much, I wonder?

    I seem to recall hearing a story that old folks are really useful in the Australian desert: they know where the water holes are during those once-in-a-lifetime droughts. I have no source for this.

  3. Cloudswrest says:

    I think a more plausible case can be made that many, many maintenance routines individually over time reach “end-of-program”, perhaps asymptotically, leading to deteriorating vitality in the individual. Identifying them and measuring each one’s current absolute and relative (to the others) performance could probably lead to an algorithmic assessment of a persons “biological” age.

  4. caethan says:

    Maybe all the immortal mutant humans are just hiding.

  5. Old people are nature’s baby sitters, letting the young people get some work done.

    Something like four or five of the oldest people in the US are African Americans, a demographic not normally known for longevity. I’d investigate these people (and pretty much anyone over the age of 100.)

    • Bryan Bell says:

      I’m not sure what the african americans would yield. It’s due to the mortality crossover. Greg previously speculated the crossover is due to the average high paternal age in africa.

    • Greying Wanderer says:

      In the urban blight the grandmothers bring up the kids while the mothers work

      cos no dads.

    • Fourth doorman of the apocalypse says:

      Depends on the technique. Seems there was high infant mortality among Chinese castrati.

    • Greying Wanderer says:

      so might a drop in testosterone have an effect?

      say a pattern of early rise to a high peak when young – for cad competition type reasons – then an above average decline for longevity?

    • ohwilleke says:

      Another approach to increasing health in the elderly which has been shown to work for reasons that aren’t entirely clear is to give them blood transfusions from young donors, something one can understandably feel ambivalent about, but whose existence suggests another window towards understanding and taming the biochemistry of aging.

  6. ohwilleke says:

    “I have never heard of any such slow-aging genetic syndrome.”

    IIRC, some Italian populations have very great longevity with a significant proportion approaching what appears to be the hard ceiling natural limit of about 116 years for women and perhaps five or ten years younger for men.

    Most other European populations overwhelmingly die when they hit what might be called the soft ceiling of about twenty years younger, although much smaller percentage of these populations than of the long lived Italian populations do manage to surpass the soft ceiling.

    I suspect that there are some similar populations in Asia that consistently have a decent percentage of people relative to other populations reach the hard ceiling.

    In the Third World, few people live in favorable enough conditions to approach their built in maximum genetic lifespans.

    My supposition is that a quite small number of genetic tweaks or drugs that act on the same pathways may extend your maximum lifespan by about twenty years, but that there is no simple solution to beat the hard ceiling on life expectancy.

    • Greying Wanderer says:

      According to google Sardinia and Okinawa have concentrations of unusual longevity. If that’s true then maybe there’s something in the food or water that does it which would be a clue to the mechanism.

    • benhardisty1 says:

      A few members of these populations only live to (apparent) maximum human age at death: none greatly exceed the 120 year ‘hard limit’ or whatever they’re calling it now. There definitely are no known slow-aging syndromes, but there are cases of bizarrely slowly developing people, such as a ‘child’ who was in her 20s or something that I read about a couple of years ago. Some researchers hope that studying rapid-aging syndromes such as progeria offer the future hope of designing genetic interventions that would slow aging for suffers, and then normal people down the road. Not sure how they ever panned out, but I will be hearing Cynthia Kenyon speak at an aging conference in a couple weeks, if anyone knows what’s going on at the intervention level it’ll be her since she’s in private industry at Google now.

  7. Fourth doorman of the apocalypse says:

    Stop the presses! Extremely high IQ black African Female athlete found at last!

    The gap can at long last be closed!

  8. Those salmon don’t die because of some kill switch. They die because they basically wore themselves out swimming upstream, pumping themselves full of steroids in order to be able to finish the journey.

    • Oops, I should have looked into this more before posting, as when I did, I found out that some of the experiments referred to involved keeping salmon in ponds where they didn’t and couldn’t swim upstream to anywhere; castration still prevented them from dying. So the gonads do seem to act as something of a kill switch in that scenario, making what I wrote too strong. Nevertheless, the point of the lethal steroid levels they dose themselves with is to reproduce, not to “make room” for the next generation. If a salmon could get upstream without killing itself, eat its fill of other salmon’s eggs and young, and return to the ocean to repeat the exercise the next year, it’d have a markedly greater chance of passing on its genes. So if dying were optional at that point, we’d see mutants living and taking over the species.

  9. Patrick Boyle says:

    It seems to me that there is an excellent chance that humans may soon attain much, much longer lifespans but only if our machine overlords allow it. If a human consciousness can be transferred to a more permanent substrate, then human life might continue indefinitely. But otherwise who cares?

    Women already live in Japan and a few other countries to ninety. But who would want to be a ninety year old woman? I would like to be a twenty five year old man again. If you can’t offer me that option – I’m not interested. Transfer my consciousness into some machine intelligence such that I think I’m tall, handsome, brilliant and strong again and I’ll be happy as a sort of video game character for thousands of years. My biological body under the best of scenarios is going to wind down in a decade or less.

    At sixty five I had everything that makes live sweet but that simply can’t last. Most never even get what I once had. Natural Selection gave me many gifts, and I’m appreciative, but now its time to transition to a new substrate that lasts longer.

  10. they are useless because of aging, not vice versa

  11. dearieme says:

    Old folk would be a disproportionate burden to wandering hunter-gatherer people. You couldn’t even send them up trees the way you could the young. They’d become less of a burden among sedentary people.

  12. kai says:

    Would looking at people with exceptionally quick aging be as informative? Like progeria? I still remember seing a child suffering from it when I was maybe 8 year old, that occured more than 30 years ago. Very marking experience….

    • ohwilleke says:

      There is research underway on that condition. See Zhang, et al., “A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.” Science (30 April 2015).

      Basically, Werner’s syndrome mutates genes responsible for a protein called WRN that governs how bundles of DNA called heterochromatin organize themselves, which causes heterochromatin to become disorganized. This phenomena is found both in Werner’s syndrome sufferers and also in people without Werner’s syndrome who are advanced in age.

      The hope, of course, is that treatments targeting heterochromatin organization could retard or reverse the human aging process.

    • benhardisty1 says:

      See above. But, yeah, that’s the thinking of some experts on the genetics of progeria. If we can first off stop sufferers from aging so rapidly, we might be on to something…

  13. MawBTS says:

    <

    blockquote>It is possible that old people were once useful (materially contributed to the fitness of near relatives), especially in preliterate days. Back the ice age climate could change rapidly (Dansgaard-Oeschger cycles) – old farts may have remembered previous climates, and that might have been useful.

    Yes, old people would have been the closest thing to books in those times. Senior members of a tribe would have been valued for their knowledge of animals, plants, landmarks, tribal relations, etc, etc.

  14. Jerome says:

    The idea that “old farts” require some evolutionary justification starts from the assumption that they do not reproduce. But that aspect of senescence requires explanation just as much as any other. Women do have a sort of “kill switch” that turns off their ability to reproduce well before everything else shuts down. Is menopause adaptive?

    • Rick says:

      Menopause probably is adaptive. This is the human equivalent of salmon dying. They sacrifice their own reproduction for that of their children’s reproduction.

  15. James Graham says:

    As mentioned in the September 7, 2006 edition of The New York Times, Norman E. Sharpless of The University of North Carolina believes aging “is a program, an anti-cancer program.” He based that conclusion on the observation of tumors and the patterns of cell division in mice.
    http://www.nytimes.com/2006/09/07/science/07stem.html?_r=3&oref=slogin&oref=slogin&

    I had previously reached a similar conclusion in expanding my idea that lethal juvenile cancer played a significant role in the evolution of complex animals, writing in my 1992 book that the idea explains “the origin and function of [Bilaterian] aging. The programmed shutdown of the cell-renewal process [was] selected to avoid cancer.” I added that since any theory of aging has an obligation to explain also its absence in many cell colonies, the verified occurrence of cancer only in Bilaterians and its apparent non-occurrence in the cell colonies is consistent with the anti-cancer adaptation idea.
    https://play.google.com/books/reader?printsec=frontcover&output=reader&id=LQ_YmCOcS3EC&pg=GBS.PP1

    Recent research with naked mole rats also seems supportive.
    http://cancerselection.blogspot.com/2013/08/do-naked-mole-rats-confirm-that_20.html

  16. Abelard Lindsey says:

    I’ve never subscribed to any of the programmed aging theories. I still think Aubrey de Grey’s theories being the cause of aging makes the most sense. I also don’t think aging is an anti-cancer adaption. If it was, the probability of cancer as one ages should either be linear or decreasing. It does not. Indeed, the probability of cancer increases with advanced age.

    • Justin says:

      I am thinking your conclusion about cancer does not follow. We don’t know what the cancer hazard curve looks like in a counterfactual human population that doesn’t age. Aging could still lower the probability of cancer at any given chronological age, it may just be that the mechanism(s) behind senescence overwhelm.

      But yeah, de Grey sounds compelling to me. Not that I’ve earned a right to an opinion on the matter 😀

      • Abelard Lindsey says:

        Aging could still lower the probability of cancer at any given chronological age, it may just be that the mechanism(s) behind senescence overwhelm.

        In which case, aging is a seriously half-assed method to control aging, as it does a piss-poor of doing so.

    • James Graham says:

      Your comment reminds me of an encounter I had shortly after my theory was accepted for publication by the Journal of Theoretical Biology. I met a man with a science doctorate and told him about my idea, that lethal cancer in juveniles played a significant role in animal evolution. He paused for a few seconds and then told me my theory was wrong because death from cancer often occurs years after an encounter with a carcinogen, too late to influence evolution. He was referring to what is called the “time bomb” phenomenon which, by the way, occurs in hamsters as well as humans. But not only does it not conflict with my theory, it actually supports it as I explain on page 135 of my book.

      https://play.google.com/books/reader?printsec=frontcover&output=reader&id=LQ_YmCOcS3EC&pg=GBS.PP1

      (Short version: Because nature protects the young, not those past the likely age of reproduction, delaying death for years or even decades makes evolutionary sense.)

      That fellow made the same mistake as you: he criticized an idea he did not understand.

      My theory says cancer and defenses against it came into existence in Bilaterians >500 mya. Because it can start only in cells that divide during the life of the animal perhaps the simplest defense against it was to minimize mitosis. Slowing down mitosis or even stopping it completely when the animal has (likely) passed reproductive age would make evolutionary sense. Cessation of cell division is the essence of programmed senescence which is why I suggested it was adopted–a very long time ago–as a cancer defense.

      As I make clear in my writings when new defenses against cancer are acquired by animal lineages those lineages might then dispense with older defenses. That seems to have happened with naked mole rats

      http://cancerselection.blogspot.com/2013/08/do-naked-mole-rats-confirm-that_20.html

      which have acquired a highly effective anti-cancer defense; it explains why they live much longer than other, cancer-experiencing, rodent species. I also think something similar happened in human evolution. The earliest primates were, apparently, lemur-like animals about the size of squirrels. Thinking probabilistically, they likely had much shorter life-spans than modern humans. Our gene pool, like that of naked mole rats, pushed back the onset of senescence as our immune systems became increasingly efficient as killers of cancer cells.

      Nothing in modern human cancer experience, including the age of human victims, conflicts with my theory. In fact, I seem to have been the first to propose an explanation for why the origin sites of most pediatric cancers differ from the adult experience. They begin in locations that have undergone recent evolutionary change: the brain, leg and arm bones (our limbs are longer than other primates’) and in white blood cells (our immune system is constantly evolving to keep up with changes in pathogens.) That part of my theory has been cited here:

      http://www.jamesgraham.bz/images/Leroi026.pdf

      here:

      http://www.jamesgraham.bz/images/Crespi_Kyle_2005_evol._biol._of_cancer.pdf

      here:

      http://www.sfu.ca/biology/faculty/crespi/pdfs/90-Crespi&SumMersTREE.pdf

      … and in a few other places.

      As for other theories of senescence, I’ll pay attention to any that also explain why many cell colonies seem immune to aging. Oak trees, bristle cone pines and other trees live for centuries and Bonner has described a huckleberry plant with an estimated age of 13,000 years.

      https://books.google.com/books?id=1n2Hv6BQHYQC&printsec=frontcover&dq=%22John+Tyler+Bonner%22&hl=en&sa=X&ei=vgSPVbnqFYv_-AGqkLjgCg&ved=0CDQQ6AEwAg#v=onepage&q=%22John%20Tyler%20Bonner%22&f=false

      In the Victorian era people kept sea anemones alive in their parlors for decades with death occurring only if someone knocked over the glass tank.

  17. Ilya says:

    @gcochran: Regarding salmon: I’ve been reading Nowak, Tarnita & Wilson paper that disputes inclusive fitness as meaningful in itself. I tend to agree.

    A behavior as strong as self-sacrifice for the sake of own children is sane. However, in eusocial creatures, methods to punish/limit defectors/cheaters have evolved (https://en.wikipedia.org/wiki/Cheating_(biology)#Cheating_in_eusocial_insects). In self-sacrificing salmon, what are the methods to punish cheaters (i.e. an individual that pretends to die, only to squeert some eggs/sperm and, instead of nobly fertilizing soil, go on to reproduce in the next cycle)?

    The unwashed masses wish to be enlightened, please!

  18. kernly says:

    Any idea why octopus die after reproducing once? Unlike with salmon there’s no argument to be made that they are feeding related offspring…

  19. If any organ or system in your body has a ceiling (even for unclear reasons), then no other system lasting longer creates any advantage. If there were a mutation that gave us a 500-year pancreas, who would ever know, and how would it persist except by accident? Modest increases in durability, or mutations which decreased premature misfunction of the pancreas might hang around and become common, but nothing beyond that.

  20. magusjanus says:

    any thoughts on this:

    http://www.hhmi.org/news/your-viral-infection-history-single-drop-blood

    In particular with regards to pathogen theory of obligate male homosexuality?

    Will popularizing something like this (or the lower cost) make establishing the link that much easier?

    • gcochran9 says:

      It might – but I don’t think it can be catching all previous infections. They were talking something like 13, and it can’t be that low a number.

    • benhardisty1 says:

      It only detects known antibodies to known viruses, and we know very few viruses compared to how many are probably out there. A friend does phage genetics, he said whenever people take buckets of sea water from somewhere no one else has before, they found so many new varieties of phage and virus and bacteria that they’ll never all be studied or characterized.

  21. Leonid says:

    If this were the case, it would be a good thing, because we could then hope to significantly extend the human lifespan just by interfering with key steps in the programmed aging mechanism.

    Aging may increase fitness on the group level but decrease it on the individual level. If so, it seems unlikely that aging can be easily switched off in humans (otherwise mutations that could do it would probably have spread a long time ago).

  22. Bob says:

    What about the rate of living theory and the heartbeat hypothesis? The idea that lifespan is determined by metabolism and that organisms have fixed numbers of heartbeats. Any validity to this?

    • benhardisty1 says:

      No, when the original studies from the 20s and 30s were repeated, but with measurements for vastly more species, the relationship wasn’t significant. The hypothesis keeps refusing to die, much like group selection! However, there does seem to be a strong role for metabolism, not 100% clear what that is though. We just know you grow slower, grow smaller at maturity but live a lot longer if your metabolism is knocked-down with an RNAi knock-down, or when a gene knocks-out is used at one allele in IGF or TOR1 or similar growth-promoting genes.

  23. Dale says:

    I’ve long favored the theory in “The Selfish Gene” (IIRC): There’s a cost to making a body that will last a long time, and given the rate of death due to unavoidable causes, there’s an optimal longevity. The general evidence is that vertebrates that are subject to little predation have longer lives than their body size would suggest, and those subject to a lot of predation have shorter lives.

    I don’t know how you’d test that. Anecdotal evidence, at least, says that longevity is significantly heritable, and there’s been experiments to breed longer-lived mice and fruit flies. But I’ve never heard of work done on humans.

  24. MawBTS says:

    I’ve long favored the theory in “The Selfish Gene” (IIRC): There’s a cost to making a body that will last a long time, and given the rate of death due to unavoidable causes, there’s an optimal longevity.

    As Greg once said, it’s as pointless as paying for a magic car that never needs servicing…and entering that car in a demolition derby.

    Or, alternately, a pornstar putting on magic makeup that never ages…and then starring in a 50 guy gangbang film.

    We live in a dangerous and unpredictable environment, and we evolved in a REALLY dangerous and unpredictable environment. Genes that extend your natural lifespan can only pay off so much when you can die unexpectedly at any time.

  25. Jeff says:

    Have you seen this woman’s work on homosexuality (A reader, Tartar at 6/5/14 10:54am calls you out.). http://www.washingtonpost.com/posteverything/wp/2014/06/04/the-science-of-sexuality-how-our-genes-make-us-gay-or-straight/

    Is her concept of a male loving allele a plausible explanation for homosexuality? She points to research showing gay genes in certain animals.

    • Fourth doorman of the apocalypse says:

      The hit on reproductive success for desiring the opposite sex is enormous.

      It is akin to the problem of Cuckoos.

      If the victim species of cuckoos have evolved strategies for dealing with a much lower hit on their reproductive success, don’t you think that selection would have dealt with the large effect that homosexuality has. Ergo, Cochran’s gay germ theory.

  26. Henk says:

    The article presents a computer model featuring perfect hunters who, if unchecked, inevitably hunt their prey to extinction (within their allocated lot on the grid), then die.

    Programmed death then seems to be beneficial by stochastically avoiding the hunt to extinction and (through the model’s spacial properties) distributing the resulting benefit to close relatives.

    But given that the mitigation is beneficial, do such critters evolve into perfect hunters in the first place? I would be interested in whether, in the same model, a species of initially lousy hunters would not just reach a limit of hunting proficiency, instead of pairing more hunting with altruistic suicide. (To be honest, not interested enough to run the simulations myself.)

    • gcochran9 says:

      I think that the whole model is nonsense. I brought it up to point out that physicists can be crazy too, although usually in their own special way. Unlike biologists, they can usually do the math – but in this problem, your only chance of making progress is if you know a lot of facts, in this case about human prehistory, human-caused extinction, the genetics of long life in humans (why no significant life-extending mutations if death is programmed?), etc.

  27. benhardisty1 says:

    A) The Gordon Research Conference on the Biology of Aging was quite interesting. One of the talks was about how germlines in fact age like any other parts of the body, but have mechanisms that periodically repair all the damage accrued over the reproductive lifespan.
    B) Disappointingly, only one talk actually discussed a drug that is in clinical trials (Phase 2 trials are now finished) as a general anti-aging treatment. It’s a sirtuin upregulator.

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