The genetics of exceptional human longevity.
How we age as individuals is no doubt a complex interaction of genetic and environmental factors. Studies of certain populations with optimal environments and health-related behaviors, as well as twin studies, suggest that the average set of genetic variations should facilitate the average person's ability to live to around age 85. Average life expectancies are lower than this because we generally fight survival advantage with bad health habits that can lead to premature aging, chronic illness, and death at a significantly younger age. Centenarians on the other hand live 15-25 years beyond what the average collection of us are able to achieve. Many of them have a history of aging relatively slowly, and either markedly delaying or even escaping lethal diseases associated with aging (Alzheimer's disease, stroke, cancer, cardiovascular disease, and diabetes). In order to live to such old age, centenarians are less likely to have genetic and environmental exposures that would cause at least lethal diseases at younger ages. Demographic selection is the drop out within a cohort, of genotypes linked to age-related lethal diseases and premature mortality as the cohort achieves older and older age. The result is a very old cohort that lacks these genotypes relative to younger age groups. Recent pedigree and molecular genetic studies indicate that scientists can use this selection to their advantage in discerning genotypes that play important roles in delaying or escaping diseases such as Alzheimer's disease, and in slowing the aging process.
Perls
Thomas
T
thperls@bu.edu
Kunkel
Louis M
LM
Puca
Annibale A
AA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008017:Life Expectancy / Q000639:trends; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D010641:Phenotype; D012727:Sex Characteristics