Between Zeus and the Salmon

Today I'll point out an open access book manuscript on the biodemography of longevity, entitled Between Zeus and the Salmon; this is a goodly amount of reading material, and will probably keep you busy for a weekend or two. It's written from the conservative mainstream point of view, which is to say that it expresses the assumptions that (a) any future change in human longevity will be incremental and small, because (b) no radical advances in biotechnology applicable to aging are waiting in the wings, and (c) manipulation of longevity-related genes to slow aging is the best way forward, even though it will be slow, hard, challenging work. This is wrong, wrong, wrong - but that's always the way of the mainstream. They are there to be surprised and disrupted by suddenly rushing technological advancement, discontinuities in the pace of progress that occur increasingly frequently in this age of ours.

If you want to understand this mainstream of longevity research and its viewpoints on present day and near future challenges in the field, however, then this is a great resource:

As I see it, for demographers today, the golden challenge is to make the right judgment call predicting our children's life spans. Will the recent pace of gains in life expectancy and active life expectancy extend to the next generation, or are we approaching the point of diminishing returns? The deep theoretical questions in the demography of mortality and aging - including the proper framework for incorporating genetic variables and cofactors into demographic models - cluster around this very practical question of prediction, whose answer some of us may live to know.

Confronting this question, the in-house tools of traditional demography - accurate accounting of vital trends and descriptive modeling of variability across time and circumstances - are indispensable but inconclusive. Knowledge of detailed mechanisms is too patchy for causal models with aggregate implications. Thus demographers are thrown back on a search for analogues. Biology is our cornucopia of analogues.

I do not want to overstate the relevance of biology to demography. Biology will not settle demographic questions directly. Finding the causes behind the leveling out of fruit-fly hazard functions after 100 days will not disclose the causes behind any leveling out of human hazard functions after 100 years. Genes promoting survival at advanced ages may be found in nematode worms without giving us any right to expect usefully close counterparts in people. Darwinian theory, for all its triumphs, is a poor basis for predicting whether women's advantage in life expectancy over men will be increasing or decreasing in 2047.

Nonetheless, biology is definitive. Experiments with laboratory organisms, genetic mapping, natural history, and evolutionary theory are defining the intellectual landscape within which demographic arguments and forecasts gain or lose their appeal. Uncertainties are so great and mortality prediction is so much a matter of bets and guesses that the powerful analogies provided by biology are the best guides we have.

But we now enter an age in which biology is increasingly ours to command - and by extension we will soon enough no longer be limited by the outcome of past evolution. By 2047, asking after the degree to which women outlive men will be something akin to asking today whether Englishmen or Frenchmen better resist scurvy. It's a question that has no relevance, buried completely by the advance of medicine and medical knowledge: by 2047, our ability to extend the human life span will dwarf any natural difference due to gender.

Nonetheless, you'll find some interesting material here on many varied topics, such as ongoing research into the genetics of human longevity:

Central to my own thinking are a pair of questions that I call the "hundreds-thousands-tens-of-thousands" questions. The first question is this: How many genes should I imagine there being whose specific effects on old-age survival are strong enough to be noticeable in a population? The second question is the converse: How many genes should I imagine typically having to act in concert to produce any one noticeable effect on old-age survival in a population?

I used to think that the answers to these questions were likely to be at the tens-of-thousands end of the scale of orders of magnitude and that the biodemography of longevity would have to become a sort of statistical mechanics before it could make sense. But I have been strongly impressed by the life of Madame Calment and the data on survival at extreme age ... Humans who make it to 110 years of age appear to have truly better further survival rates than those who make it to 95 or 100. No obvious behavioral and environmental determinants of extreme survival have turned up as yet. It therefore seems as if there could be a relatively small number of bad genes - hundreds, not tens-of-thousands - which one has to not have in order to survive ad extrema.

The topic of late life plateaus in mortality crop ups again here - that mortality rates stop advancing at some point very late in life, and stay high but static. This seems to be an idea that has gathered more attention from the broader research community over recent years. Certainly the evidence for this phenomenon in flies is iron-clad, but there is skepticism and debate over what sort of interpretation is supported by the far more limited human data.

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