Aging Aging

Mutation and the Aging Process 17913Mutation and the Aging ProcessMutant Frequency at the HPRT Gene Locusas a Function of Age in HumansYvonne A. Barnett and Christopher R. Barnett1. IntroductionAging is a complex, biological process that is contributed to by intrinsic(genetic) and extrinsic (nutrition, infectious agents, xenobiotic exposure, etc.)factors (1). Several decades ago it was first proposed that instabilities in theorganization and expression of the genetic material was likely to be involved inthe aging process (reviewed in ref. 2). Indeed, since that time much experimentalevidence has been published that details increases in DNA damage (3–8)and mutation (8,9–15) in various cells and tissues with age in humans.Organisms are continuously exposed to a variety of extrinsic biological,chemical, and physical factors that may alter the structure and therefore havethe potential to modify in vivo the function of a wide range of biomolecules,including DNA (16–20). If modifications to the structure of DNA are not recognizedand removed/repaired, then mutations may result. Mutations in essentialgenes, in association with the age-related alterations in proteins and lipids,may result in the degradation of structural elements within the cells, tissues,and organs of the body, leading to a decline in biological function and eventuallyto disease and death (1,20,21). There has been a large numerical growth inthe number of older people around the world, due in large part to improvementsin environmental conditions such as nutrition, housing, sanitation, andmedical and social services. In industrialized countries with low fertility levelsthis has resulted in large gains in median population ages. In the 1900s themaximum life expectancy was around 47 yr, but now this has risen to a mean ofapprox 75 yr (22). Further, due in large part to improvements in environmentalFrom: Methods in Molecular Medicine, Vol. 38: Aging Methods and ProtocolsEdited by: Y. A. Barnett and C. R. Barnett © Humana Press Inc., Totowa, NJ179