I.  Introduction

    A.  Definition of Senescence:  Senescence (or aging) is a persistent decline in age-specific fitness components of an organism due to
             internal physiological deterioration. (From M. R. Rose)

    B.  Recoginzing senescence

        1.  A survivorship curve,  l(x), plots the probability that an indivdual is still alive as a function of
             age, x:
 

All figures, unless otherwise indicated, are from M. R. Rose.  1991.  Evolutionary Biology of Aging.  Oxford Univ. Press, New York.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

II.  Genetic Variation for Lifespan

    A.  Strain Differences

        1.  Example:  Ganetzky and Flanagan.  1978.  On the relationship between senescence and
             age-related changes in two wild-type strains of Drosophila melanogaster.  Exp.
             Gerontol. 13: 189-196.
 
 

        1.  Example:  selection for prolonged lifespan in Drosophila subobscura (Wattiaux, J. M.
             1968.  Cumulative parental effects in Drosophila subobscura.  Evolution 22: 406-421.)

III.  The Issue

   A..  Results of these genetic analyses of senescence raise a fundamental evolutionary question:  if species
          harbor genetic variants for which senescence is postponed, why has natural selection not caused
          these variants to become fixed?  i.e., why have organisms not evolved longer life spans?

   B.   Basic principle (age-intensity principle):  the intensity of selection acting on a trait late in life is expected to be lower than
          the intensity of selection acting on a trait expressed early in life.
 
 

IV.  Age-Intensity of Principle

    A.  Restatement of the principle

    B.  Illustration of principle.

    C.   Intuitive explanation of principle:

            a.  when a mutation affects survival late in life, most individuals are dead before the
                 effects of the allele are expressed, and therefore a  beneficial allele can only increase
                 the fitness of a small fraction of the individuals that carry it.
            b.  By contrast, when a mutation affects survival early in life, most individuals carrying
                 the mutant allele are alive when the allele is expressed and thus benefit from having
                 that allele.

V.  Evolutionary Theories of Senescence

    A.  Two general theoretical explanations for the evolution of senescence:

        1.  Antagonistic pleiotropy theory

        2.  Mutation acumulation theory

    B.  Antagonistic pleiotropy theory (Due to Medawar and Williams)

        1.  Explanation

        2.  Experimental evidence for antagonistic pleiotropy--genetic correlations
             (Rose and Charlesworth.  1981.  Genetics 97: 173-186.)

        3.  Experimental evidence for antagonisitc pleiotropy--selection experiments

             ( Rose. 1984.  Evolution 38: 1004-1010.)
 

    C.  Mutation acumulation theory. (Due to Medawar)

        1.  Explanation

        2.  Evidence for mutation accumulation: increased genetic variation in age-specific fitness with
             age.  (Rose and Charlesworth 1981.)
 
 

        3.  Experimental evidence for mutation accumulation: selection experiments.

            a.  Logic and protocol of the experiment:

            b.  Example:  Mueller, L. D.  1987.  Proc. Nat. Acad. Sci. 84: 1974-1977.

    D.  Conclusions

        1.  Analysis of genetic variation for senescence in Drosophila indicates that both antagonistic
             pleiotropy and mutation accumulation contribute to senescence.

        2.  Little information is available for other oragnisms.

IV. Implications of Evolutionary Theories of Senescence

    A.  The major cause of senescence is the decreasing strength of selection as organisms age, which allows
          mutations causing reduced late fitness to increase in frequency or even become fixed.  (Note that this
          is true regardless of whether antagonistic pleiotropy or mutation accumulation applies.)

    B.  Implies that there will be no "general cause" of senescence that acts across species, or even across
          populations.

        1.  In any species or population the exact causes of senescence will depend on what mutations
             having deleterious effects on late fitness increase in frequency, and what characters those
             mutations affect.

        2.  Also implies that senescence in a particular organism may have multiple causes, representing
             different characters affected by different deleterious mutations contributing to senescence.

    C.  Suggests that studying the "cause" of senescence in non-human animals will not be informative
          directly about the causes of senescence in humans, and thus will not provide direct information on
          the types of medical intervention that will be needed to eliminate senescence in humans.

    D.  Nevertheless, exploration of the causes of senescence in other organisms may indirectly benefit
          research in human gerontology by leading to the development of a robust research protocol that
          can be applied to the study of human senescence.

    E.  Hope for a "magic bullet" cure of senescence, however, are slim, because evolutionary considerations
         suggest that once a cure is developed for one senescence factor and lifespan is extended somewhat,
         other senescence factors will kick in to limit lifespan.