Does genotypic sex have a direct effect on longevity?
Females of the human species live longer than males, and the longevity differential is probably not entirely explained by reasons which are presently obvious. Genotypic sex has long been suspected to affect longevity to the advantage of the female. Several recent findings about the X and Y chromosomes must be reckoned with in considering determinants of longevity which derive from genotypic sex. The advantages of having two X chromosomes are apparent, notwithstanding X-chromosome inactivation. Not only can some cells compensate for biosynthetic deficiencies of others, but also cell selection according to which X chromosome is active can occur during development according to cell viability and proliferative capacity. It has recently been observed that at least some genes on inactive X chromosomes are reactivated late in life. Details of the reactivation process must be studied to determine its significance and the effects of the process on late life survival. The recent mapping of the catalytic polypeptide of DNA-polymerase-alpha to the X chromosome calls attention to a new property of the genotype which could affect the basic ability of cells to proliferate. It is likely that this enzyme, perhaps in concert with DNA-polymerase-delta, is required for DNA replication, suggesting that two alleles for this enzyme and cell selection within the female phenotypic mosaic for DNA replication may provide a sex-linked determinant of cell proliferation which could be advantageous in late life. Much remains to be learned about the Y chromosome, although there are early results consistent with a determinant of longevity on that chromosome which operates to the male disadvantage and probably does not involve sex hormones. The genotype may be a significant determinant of longevity in humans even if it does not appear to be so in non-human animals, because causes of death are different. Determinants of longevity are based on susceptibility or vulnerability to the causes and diseases of mortality, and these differ in different species.
Smith
D W
DW
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611.
Warner
H R
HR
D005260:Female; D005838:Genotype; D006801:Humans; D008136:Longevity; D008297:Male; D012737:Sex Factors