Genetics and Evolution - The Role Of Genes Inexceptional Longevity

The number of centenarians (people 100 years or older) in the population is increasing by 8% per year, significantly more rapidly than the annual 1% increase in population. In the United States at the turn of the twentieth century about one in 100,000 people were centenarians; by 2002 the rate had risen to one in 10,000. This remarkable increase probably results from improved survival rates in early childhood and beyond age eighty. Public health measures have eliminated many of the infectious diseases that produced a 25% infant mortality rate until the turn of the twentieth century. Effective treatment of reversible causes of death in older adults has increased longevity. The precise contributions of environmental influences and genes to attaining exceptionally long life spans are unknown, but there is increasingly strong support for the role of genes in exceptional longevity.

Boston University Medical School researchers Thomas Perls, Louis Kunkel, and Annibale Puca reviewed available data about genetics and aging in "The Genetics of Exceptional Human Longevity" (Journal of the American Geriatrics Society, vol. 50, no. 2, February 2002). Distinguishing between the genetics of aging and the genetics of exceptional longevity, the investigators found that studies of twins indicate that the average set of genetic variations facilitates the average human's ability to live well into his or her eighties. Other studies have shown that taking full advantage of this average genetic capacity results in spending most of the later years in good health. Perls, Kunkel, and Puca observed, however, that many people defeat their genetic capacity by making poor choices, such as smoking, overeating, and not exercising, in terms of health and lifestyle. These unhealthy choices substantially reduce average life expectancy and increase the time spent in poor health.

To live past the eighties, life span experiments in lower organisms and mammals as well as population and molecular genetic studies of centenarians suggest that genetic factors make strong contributions to exceptional longevity. These factors are likely to govern the physiology of aging, which in turn influences susceptibility to age-related diseases. Perls, Kunkel, and Puca described the centenarian phenotype as markedly delaying or even escaping age-associated diseases. They concluded that the combination of the absence of genetic variations that predispose disease and the presence of variations that bestow disease resistance (longevity-enabling genes) probably confers the exceptional survival advantage.

Although they concede that aging and susceptibility to diseases associated with aging are very likely influenced by thousands of genes, by studying families with the long-lived phenotype the researchers attempted to answer the question of whether such longevity is attributable to chance or whether genetics play a significant role. Perls, Kunkel, and Puca found evidence indicating the significant likelihood that a gene or genes in a specific location exert a substantial positive influence on the ability to achieve exceptional old age.

Speculating about the evolutionary force that motivated development of longevity-enabling genes, Perls, Kunkel, and Puca hypothesized that it may have been a response to pressure to prolong fertility, enabling women to have more offspring. They observed that increased life span is associated with longer periods of reproductive fitness in species such as fruit flies and primates.