Much research interest, and recently even commercial interest, has been predicated on the assumption that reasonably closely-related species – humans and mice, for example – should, in principle, respond to ageing-retarding interventions with an increase in maximum lifespan roughly proportional to their control lifespan (that without the intervention). Here, it is argued that the best-studied life-extending manipulations of mice are examples of a category that is highly unlikely to follow this rule, and more likely to exhibit only a similar absolute increase in maximum lifespan from one species to the next, independent of the species’ control lifespan. That category – reduction in dietary calories or in the organism’s ability to metabolize or sense them – is widely recognized to extend lifespan as an evolutionary adaptation to transient starvation in the wild, a situation which alters the organism’s optimal partitioning of resources between maintenance and reproduction. What has been generally overlooked is that the extent of the evolutionary pressure to maintain adaptability to a given duration of starvation varies with the frequency of that duration, something which is – certainly for terrestrial animals and less directly for others – determined principally by the weather. The pattern of starvation that the weather imposes is suggested here to be of a sort that will tend to cause all terrestrial animals, even those as far apart phylogenetically as nematodes and mice, to possess the ability to live a similar maximum absolute (rather than proportional) amount longer when food is short than when it is plentiful. This generalization is strikingly in line with available data, leading (given the increasing implausibility of further extending human mean but not maximum lifespan in the industrialized world) to the biomedically and commercially sobering conclusion that interventions which manipulate caloric intake or its sensing are unlikely ever to confer more than 2 or 3 years’ increase in human mean or maximum lifespan at the most.

Keywords:
Life expectancy, Caloric restriction, Nutrient sensing, Life-extension drugs
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© 2005 S. Karger AG, Basel
2005
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