Mitochondrial DNA Heteroplasmy Associations With Neurosensory and Mobility Function in Elderly Adults

作者：Tranah Gregory J^*; Yaffe Kristine; Katzman Shana M; Lam Ernest T; Pawlikowska Ludmila; Kwok Pui Yan; Schork Nicholas J; Manini Todd M; Kritchevsky Stephen; Thomas Fridtjof; Newman Anne B; Harris Tamara B; Coleman Anne L; Gorin Michael B; Helzner Elizabeth P; Rowbotham Michael C; Browner Warren S; Cummings Steven R

来源：Journals of Gerontology Series A-Biological Sciences and Medical Sciences, 2015, 70(11): 1418-1424.

DOI：10.1093/gerona/glv097

• Mitochondrial DNA
• Heteroplasmy
• Cognition
• Vision
• Hearing
• Mobility

Background. Mitochondrial DNA ( mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease. Methods. We examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study. Results. Elevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m. 10158T> C with Modified Mini-Mental State Examination score ( p =.009); m. 11778G> A with contrast sensitivity ( p =.02); m. 7445A> G with high-frequency hearing ( p =.047); and m. 5703G> A with 400 m walking speed ( p =.007). Conclusions. These results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments.

• 出版日期2015-11