Richard M. Cawthon, M.D., Ph.D.
Research Associate Professor

Contribution to Society

According to some estimates, 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.

Research Summary

We are studying the genetics of human aging. 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, we will measure, 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 will be examined in a large genealogical database. First we 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.

Recent Publications

Hasstedt SJ, Camp NJ, Hopkins PN, Coon H, McKinney JT, Cawthon RM, Hunt SC (2004) Model-fitting and linkage analysis of sodium-lithium countertransport. Eur J Hum Genet. [Epub ahead of print]

Hunt SC, Coon H, Hasstedt SJ, Cawthon RM, Camp NJ, Wu LL, Hopkins PN. (2004) Linkage of serum creatinine and glomerular filtration rate to chromosome 2 in Utah pedigrees. Am J Hypertens. 17(6):511-5.

Camp NJ, Hopkins PN, Hasstedt SJ, Coon H, Malhotra A, Cawthon RM, Hunt SC (2003) Genome-wide multipoint parametric linkage analysis of pulse pressure in large, extended utah pedigrees.
Hypertension 42(3):322-8. Epub 2003 Jul 21.

Cawthon RM, KR Smith, E O'Brien, A Sivatchenko, and RA Kerber (2003) Association between telomere length in blood and mortality in people aged 60 years or older. The Lancet 361(9355):393-5

Cawthon RM (2002) Telomere measurement by quantitative PCR. Nucleic Acids Res. 30(10):e47.

Kerber RA, O'Brien E, Smith KR, Cawthon RM (2001) Familial excess longevity in Utah genealogies. J Gerontol A Biol Sci Med Sci. 56(3):B130-9.

NIA Aging and Genetic Epidemiology Working Group (includes Cawthon, R.) (2000) Genetic epidemiologic studies on age-specified traits. Am J Epidemiol. 152(11):1003-8.

Cawthon R, Smith KR, Mineau GP, Kerber R, and O'Brien E (1999). Fertile Older Women Have Long-Lived Siblings: Toward a Genetic Analysis of Late Fertility and Longevity. Keystone Symposia on Molecular & Cellular Biology: Aging: Genetic & Environmental Influences on Life Span.

Smith KR, Mineau GP, Kerber R, O'Brien E, and Cawthon R (1999) Siblings of Late Fertile Women Live Longer. Population Association of America Annual Meeting, New York City, Session 704: The Biodemography of Aging.

Cawthon R, Kerber RA, O'Brien E, and Smith KR (1999) Genealogical data supports mitochondrial inheritance of longevity. The Gerontologist 39: Special Issue I: p. 2.