Caloric Restriction and the
Case for an Adaptive Theory of Senescence

Joshua Mitteldorf
Dept of Biology, Leidy Laboratory
University of Pennsylvania
Philadelphia, PA 19104-6018
josh@forum.swarthmore.edu

Synopsis

Laboratory animals maintained on a diet restricted in calories (CR) live longer than ad libitum fed animals, and many of the physiological markers of senescence appear on a delayed schedule. On its face, this effect attests to the plasticity of senescent processes under genetic control, and thus supports the notion of senescence as an adaptation. The difficulty of reconciling CR data with prevailing theories of the evolution of senescence is highlighted, and other failings of these theories are summarized. An adaptive model of senescence solves these problems, but detailed implementation remains a substantial challenge.



Outline
1.  In animal studies, caloric restriction leads to slower aging. This is an evolutionary adaptation.
2. The ability of the metabolism to extend life under caloric stress suggests that the metabolism is "holding back" when not stressed.
3. There are three prevailing theories of the evolution of senescence.
    A. Disposable Soma: There is not enough food energy both to completely repair ravages of age and also to support maximal fertility.
        *  Then why is metabolism able to extend life with less food energy?
    B. Antagonistic pleiotropy: genes that enhance fertility have the side-effect of causing senescence.
        *  Then why, in laboratory evolution experiments, can animals be bred for longevity without sacrificing fertility?
    C. Accumulated mutations: The genes causing senescence are recent, chance mutations that natural selection has not yet had a chance to clear from the genome.
        *  Then what is the explanation for the CR effect?
        *  And why have senescence genes been conserved over evolutionary eons?
4. Telomeres control a form of senescence in single-celled animals. It is clear from their mechanism of operation that this is neither a chance mutation nor a pleiotropic side-effect.
5. Other evidence for an adaptive theory of senescence:
    *  Senescence is not gradual, but like a switch turned off until midlife.
    *  Evidence for programmed death in salmon and annual plants.
6. Why an adaptive theory of senescence requires group selection.
    *  Difficulty of a group selective model for senescence.
    *  Reasons to think these difficulties may be overcome.
References.