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Mitochondrial DNA Mutations and Apoptosis in Mammalian Aging

¹ Department of Genetics and Medical Genetics, University of Wisconsin, Madison, Wisconsin and ² Biochemistry of Aging Laboratory, Institute on Aging, Department of Aging and Geriatric Research, College of Medicine, University of Florida, Gainesville, Florida

Requests for reprints: Tomas A. Prolla, Department of Genetics and Medical Genetics, University of Wisconsin, 425-G Henry Mall, Madison, WI 53706. E-mail: taprolla{at}wisc.edu.

Mutations in mitochondrial DNA (mtDNA) accumulate during aging, but their significance to longevity and age-associated disease has been uncertain. Recently, in support of the hypothesis that mtDNA integrity is important, we have shown that age-associated diseases arise more rapidly in mice where mtDNA mutations and increased levels of apoptosis occur at higher rates than normal due to expression of an error-prone mtDNA polymerase. Further studies in this model may provide deeper insights into the relationship between mitochondria, aging, and susceptibility to age-associated diseases, such as cancer. (Cancer Res 2006; 66(15): 7386-9)

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