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18 Genetics of Exceptional Longevity

Thomas T. Perls, Paola Sebastiani


Centenarians maintain their good health and ability to function independently often until the last few years of their lives (Hitt et al. 1999). Most subjects experience a decline in their cognitive function only in the last 3–5 years of their lifetime (Silver et al. 2001). Thus, these individuals are a human model not only of longevity, but also of the delay or escape of age-related disability and various age-related diseases.

The compression of disability of centenarians toward the end of their very long lives is likely due to the phenomenon of demographic selection. Demographic selection describes the dying off of individuals prone to diseases that typically peak in incidence in the sexagenarian through octogenarian years, thus leaving behind a cohort of select survivors. The observation by some research groups that the incidence of Alzheimer’s disease (AD) plateaus at very old ages is consistent with this phenomenon. Ritchie and Kildea (1995) performed a meta-analysis of nine epidemiological studies, finding that the rate of increase in dementia prevalence fell off among octogenarians and plateaued at approximately 40% at age 95. In a longitudinal study of older people living in Cache County, Utah in the United States, the incidence of both dementia and AD increased almost exponentially until ages 85–90 but declined after age 93 for men and age 97 for women (Tschanz et al. 2005). A genetic example of demographic selection is the decreased frequency of the apolipoprotein E-ɛ4 (ApoE-ɛ4)...

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