The mitochondrial and nuclear genomes, often described as the master blueprints for life, accumulate damage during normal aging, and the levels of damage vary significantly among age-matched individuals; yet the proportion of the variation in age at death in the elderly attributable to loss of genomic integrity is largely unknown. To facilitate large-scale epidemiologic studies to investigate this question, we propose to develop several novel quantitative polymerase chain reaction (QPCR) based assays for various classes of DNA damage in the mitochondrial genome and at the telomeres of the nuclear genome, and to test the relevance of each class of damage to aging and longevity in two populations, one representative of the general population, and the other selected for familial longevity within mitochondrial lineages. These studies will test the prediction that lower levels of DNA damage are associated with living longer, and the prediction that heritable mitochondrial genomes that contribute to familial longevity produce lower levels of DNA damage than control mitochondrial genomes. Such results would strongly support the hypothesis that somatically acquired DNA damage is a major cause of senescence, which is at least in part under mitochondrial genetic control. This research is of great importance to public health, because it may lead to the development of tests to determine an individual's rate of aging. Once the rate of aging can be accurately measured, it will then be possible to test the effectiveness of many proposed medical interventions to slow aging. Therefore, this research is likely to speed the development of medical interventions that slow aging and extend the duration of healthy adult life. ? ? ?
| Kerber, Richard A; O'Brien, Elizabeth; Boucher, Kenneth M et al. (2012) A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci. PLoS One 7:e34746 |
| Kerber, Richard A; O'Brien, Elizabeth; Cawthon, Richard M (2009) Gene expression profiles associated with aging and mortality in humans. Aging Cell 8:239-50 |
| Cawthon, Richard M (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Res 37:e21 |
