The biodemography of variation in human frailty.

A population is composed of individuals who are heterogeneous in their susceptibility to death and disease. This heterogeneity is reflected in the age-specific incidence or mortality (hazard) function. This variation has typically been hidden--that is, not measured directly--and has generally been modeled in a purely empirical statistical way, because there is no theory in demography for the distribution of frailty. A substantial fraction of variation in frailty, however, has an underlying genetic basis, for which there is a formal theory. This theory, based on evolutionary biology and on the nature of mendelian transmission, provides prior constraints on the distribution of variation in the population as well as providing methods for identifying genes involved in many important diseases. The accumulating effects of environmental exposures with age are another major component of variation in frailty. In some important instances, this variation and its effect on the age-specific hazard function can also be understood in terms of cause-specific biological processes. These biological considerations may enable demographers to model frailty, and thus mortality, in a better way.