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Attaining age 100 is a rare event in industrialized nations, occurring in 1 person per 10,000 in the population. Becoming a centenarian does not appear to be rare because the individual genetic or behavioral factors (such as specific genetic polymorphisms or lack of specific toxic exposures) that enable such longevity are rare, but rather because having the adequate combination of these factors is rare.

To live beyond the octogenarian years, population and molecular genetic studies of centenarian sibships indicate that genetic factors play an increasingly important role as the limit of life span is approached. These factors are likely to influence basic mechanisms of aging that in turn broadly influence susceptibility to age-related illnesses. Lacking genetic variations that predispose to disease as well as having variations that confer disease resistance (longevity enabling genes) are probably both important to achieving exceptional old age. The AGE (aging, genetics, environment) nomogram is introduced as an illustrative construct for understanding the influence of environmental and genetic factors on survival to various ages, depending on variations in the hypothesized relative importance of genes and environment to longevity. The rapid rise in the incidence of centenarians could indicate that many more people than we originally thought have the optimal set of genetic factors necessary to get to 100 and beyond. Recent studies indicate the likelihood that such factors will be elucidated in the near future.

With the ample gene sequence information that has become available with the human genome project virtually completed, it has become possible to identify functional gene variants and their frequencies in elderly populations with different aging-related characteristics. Such a genetic epidemiological approach could lead to new insights with respect to the basic mechanisms of aging and longevity as well as the identification of new targets to prevent or retard some of the late-age adverse effects. Using our recently developed two-dimensional gene scanning (TDGS) technology platform we demonstrate the feasibility of this approach by screening two different populations of centenarians for polymorphic variation in the BRCA1 breast cancer susceptibility gene, one of the many genes involved in genome maintenance. The initial results obtained with this approach suggest differences in BRCA1 genotype frequencies between the centenarian populations and controls.