ABIOTROPHIC GENE-ACTION IN HOMO-SAPIENS - POTENTIAL MECHANISMS AND SIGNIFICANCE FOR THE PATHOBIOLOGY OF AGING

A subset of genetic loci of Home sapiens are reviewed that: 1) have th e potential for allelic variation (either mutation or polymorphism) su ch that degenerative and/or proliferative phenotypic aberrations may b e of relatively late onset ('abiotrophic'); 2) have phenotypic feature s which overlap, to some extent, with those of important age-related d isorders of man (many of which are systematically tabulated in this re view); 3) have had significant characterization at the biochemical gen etic level. The ascertainment bias of physicians to discover strong ph enotypic effects ('non-leaky' mutations) obscures the fact that, for m any such instances, there exist numerous other alleles of lesser effec ts, including those whose gene actions probably escape the force of na tural selection. The patterns of 'normal' aging in Homo sapiens are qu ite variable and, hence, difficult to define. It seems likely that the 'wild-type' alleles of a number of loci will also be found to have an tagonistic pleiotropic effects that contribute to the syndromology of senescence in our species.