Richard Cawthon, MD, Ph.D. is Research Associate Professor of Human Genetics in the Department of Human Genetics at University of Utah. He works on the genetics of longevity in human populations as well as on telomeres. Quoting him verbatim, slowing the rate of aging just enough to postpone the age of onset of multiple age-related chronic diseases by two to three years would save hundreds of billions of dollars in health care costs; furthermore, lowering age-specific mortality rates from multiple causes by slowing the rate of aging may be easier to achieve than lowering them to the same extent by developing a separate, more specific intervention for each of a multitude of age-related life-threatening diseases of which atherosclerotic heart disease, cancer, stroke, lung infections, and chronic obstructive pulmonary disease are among the most common. Richard's lab is studying the genetics of human aging for these reasons. Different physiological functions within the same individual decline at different rates with age, and the magnitude and rank order of these functional declines vary among individuals. These dichotomies suggest that there are two or more distinct processes of senescence. On the other hand, a single environmental intervention, restriction of calories in the diet, has been shown to extend life span and postpone the age of onset of multiple signs of senescence in every species tested to date, including mammalian species. Furthermore, mutations in any one of several genes of the nematode worm C. elegans approximately double its life span, and two of these genetic alterations combined in the same animal increase life span five-fold. Therefore, while aging is likely to be complex, with multiple environmental and genetic factors influencing it, it is reasonable to search for single genes in the human that simultaneously promote longevity and slow senescence. To look for genes that regulate senescence, the lab team is measuring, in 40 large Utah families (the Utah Genetic Reference Families), several traits that change with age beginning in young adulthood and that show increasing variation among individuals as the age of the tested population increases. This is the behavior expected if the rate of change of the trait (its rate of senescence) varies among people. Examples of such traits are shortening of chromosomal telomeres, somatic mutations in mitochondrial DNA, and declines in lung function. Quantitative traits that do not change dramatically with age but vary in tandem with age-specific mortality rates from each of two or more causes will also be examined, since such traits may be markers of a fundamental aging process; examples are peripheral blood leukocyte counts and resting heart rates. Once the traits have been quantified in individuals, genetic linkage analyses can proceed rapidly and with great power, because thousands of genetic markers have already been typed in the families being studied. To look for genes associated with longevity, patterns of longevity in families are being examined in a large genealogical database. First they will test whether some longevity follows maternal lineages, a result that would be consistent with a hypothesis that heritable mitochondrial genetic variants contribute to longevity. Mitochondria from any maternal lineages of interest will be collected for studies of function and for analysis of DNA sequence. Second, additional extended pedigrees will be identified in which the incidence of longevity is much higher than in the general population. DNA from very long-lived members of these families will be used in linkage analyses to investigate involvement of selected candidate genes, among them the human homologs of loci that are capable of conferring longevity in other species.