Longevity: Is Everything Under Genetic Control? An Inquiry Into Non-genetic and Non-environmental Sources of Variation

Abstract

In this essay, I inquire about little explored sources of non-genetic factors in individual life spans that are displayed between individuals with identical genotypes in controlled laboratory environments. The numbers of oocytes found in the ovaries of inbred mice, for example, show a > 5-fold range between individuals. Smaller, but still extensive variations are also indicated for hippocampal neurons. These variations in cell number can be attributed to stochastic processes during organogenesis, i.e. “developmental noise in cell fate determination.” They may be of general importance to functional changes during aging, as argued for reproductive senescence in females which is strongly linked to the time of oocyte depletion. More generally, I hypothesize that variations in cell numbers during development result in individual differences in the reserve cell numbers which, in turn, set critical thresholds for dysfunctions and sources of morbidity during aging. Thus, future studies on the nongenetic causes of variations in longevity could address developmental noise leading to variations in cell numbers, the external pre- and postnatal environments, and their interactions with the genome throughout the life span.