Evolutionary theories of aging, as applied to lifespan extension

Prominent biogerontologist and evolutionary biologist Michael Rose (recently named the chief scientific officer of the Biogerontology Research Foundation) has reviewed the decades-old interplay between evolutionary theories of aging and efforts to extend animal lifespans.

In the article, Rose critically evaluates several of the assumptions underlying SENS (Strategies for Engineered Negligible Senescence) as formulated by anti-aging activist Aubrey de Grey, placing them in the context of demographic and population-biological observations. Ultimately, Rose concludes that life-extension therapeutics must address the issue of age-specific adaptation in order to be effective (link; emphasis below is mine):

Making SENSE: Strategies for Engineering Negligible Senescence Evolutionarily

Thirty years ago, in 1977, few biologists thought that it would be possible to increase the maximum life span characteristic of each species over the variety of environmental conditions in which they live, whether in nature or in the laboratory. But the evolutionary theory of aging suggested otherwise. Accordingly, experiments were performed with fruit flies, Drosophila melanogaster, which showed that manipulation of the forces of natural selection over a number of generations could substantially slow the rate of aging, both demographically and physiologically. After this first transgression of the supposedly absolute limits to life extension, it was suggested that mammals too could be experimentally evolved to have greater life spans and slower aging. And further, it was argued that such postponed-aging mammals could be used to reverse-engineer a slowing of human aging. The subsequent discovery and theoretical explanation of mortality-rate plateaus revealed that aging was not due to the progressive physiological accumulation of damage. Instead, aging is now understood by evolutionary biologists to arise from a transient fall in age-specific adaptation, a fall that does not necessarily proceed toward ineluctable death. This implies that SENS must be based on re-tuning adaptation, not repairing damage. As evolutionary manipulation of model organisms shows us how adaptation can be focused on engineering negligible senescence, there are thus both scientific and practical reasons for making SENS evolutionary; that is making SENSE.

In the evolutionary view, increasing risk of mortality is the consequence of a failure to adapt to the selection-pressure landscape specific to a particular age; because post-reproductive lifespan is largely (but not always) masked from selection, it is easy to see how such age-specific failures of adaptation might occur. The “mortality plateaus” to which the author refers are life-history periods of constant, rather than increasing, mortality risk. Rose argues that the existence of these plateaus in the survival curves of many species imply that accumulation of irreparable damage is — at the very least — not the whole cause of aging. Therefore, the argument goes, reversing this damage cannot be sufficient to prevent or reverse aging as such.

Point of clarification, since I suspect that some confusion will arise: The point of the “E” in Rose’s “SENSE” is not that we must rely on evolutionary timescales in order to extend longevity, or that slow incremental change is our best hope. Rather, Rose’s point is that successful lifespan extension must include countermeasures against the molecular, cellular and systems-level mechanisms that explain and determine age-specific decreases in fitness (or, conversely, exploit the mechanisms that result in mortality plateaus). In the final analysis, the paper does not argue against the importance of accumulated damage so much as its exclusive primacy in the cause (and, therefore, remedy) of aging.

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6 comments

  1. I think that there might well be an overall tendence to inherit post-reproductive lifespan in social beings. Longer lives means that veteran members of the social structure can stay around for longer providing the benefits of their experience to their offspring. Which should result in them having better chances of survival. (Personal opinion based on observation of anecdotal data. But with humans at least it fits.)

  2. All:

    I find Dr. Rose’s ideas about lifelong metabolic adaptations fascinating, but do not believe that they actually underlie biological aging in a way that is not ultimately mediated through the kind of cellular and molecular damage that SENS (and the biogerontological mainstream) accepts, and whose repair, removal, replacement, or rendering harmless forms the basis for SENS as an intervention platform.

    Before this specific controversy arose, Dr. de Grey had already offered what appears to be a quite adequate rebuttal to the key basis for Rose’s thesis (the basis for the late-life plateau in mortality rates):

    de Grey ADNJ. Critique of the demographic evidence for “late-life non-senescence”. Biochem Soc Trans 2003; 31(2):452-454. PDF:
    http://www.mfoundation.org/files/sens/manu18.pdf

    de Grey ADNJ. Overzealous maximum-likelihood fitting falsely convicts the slope heterogeneity hypothesis. Exp Gerontol 2003; 38(8):921-923. PDF:
    http://www.mfoundation.org/files/sens/muelrep.pdf

    de Grey ADNJ. Models on trial: falsifying overstated claims of generality does not falsify correctly-stated ones. Exp Gerontol 2004; 39(3):453. PDF:
    http://www.mfoundation.org/files/sens/Roserep2.pdf

    Dr. de Grey suggested two ways that Drs. Mueller and Rose could “identify robust evidence against the slope heterogeneity hypothesis [Dr. de Grey’s alternative interpretation of the phenomenon] as compared to their model” using tools available to them; they have not yet taken up these suggestions, nor provided any other clear rebuttal to Dr. de Grey’s more parsimonious explanation.

    -Michael

  3. Good point, Mstudent. The same should be true for chimps and gorillas, social apes.We need to get more accustomed to out of the box evolutionary reasoning.

    I haven’t read Rose’s article, but the whim that survival curve “plateaus” imply that “aging” is not happening during those time periods, lacks depth.

  4. That isn’t his point, exactly. Rose’s point is that in a model where accumulation of damage is constant or accelerating, and that this is the primary cause of aging (where “aging” is a time-dependent loss of fitness), then there shouldn’t be mortality plateaus.

    I’d recommend reading the article; lacking depth and acting on whim are problems that Rose definitely does not have. If you’d like, I can forward you a copy of the PDF –let me know.

  5. Thanks for the clarification. I had inferred Rose’s point from your earlier posting, exactly as you confirm in comments. Your comment #2 saves me the trouble of reiterating the points de Grey has already made–and as you say, Rose has not responded to them.

    I do not know Rose and have no professional overlap or interaction with him. My spontaneous and quite innocent impression is that this entire issue gives the appearance of a bit of hand-waving by Rose to make sure that no one is forgetting that he is here.

  6. reverse engineer longevity changes in mammals? that would take an eternity… i don’t have an eternity… but the idea is good..

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