期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-018-30255-6
关键词
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资金
- Intramural Research Program of the NIH, National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]
- National Institutes of Health [R01-AG028050, R03-AG032498, R01-NR012459, Z01A6000932, R01-HL121023]
- Research and Education Leadership Committee of the CPMC Foundation
- L.K. Whittier Foundation
Mitochondria contain many copies of a circular DNA molecule (mtDNA), which has been observed as a mixture of normal and mutated states known as heteroplasmy. Elevated heteroplasmy at a single mtDNA site, m.3243A > G, leads to neurologic, sensory, movement, metabolic, and cardiopulmonary impairments. We measured leukocyte mtDNA m.3243A > G heteroplasmy in 789 elderly men and women from the bi-racial, population-based Health, Aging, and Body Composition Study to identify associations with age-related functioning and mortality. Mutation burden for the m.3243A > G ranged from 0-19% and elevated heteroplasmy was associated with reduced strength, cognitive, metabolic, and cardiovascular functioning. Risk of all-cause, dementia and stroke mortality was significantly elevated for participants in the highest tertiles of m.3243A > G heteroplasmy. These results indicate that the accumulation of a rare genetic disease mutation, m.3243A > G, manifests as several aging outcomes and that some diseases of aging may be attributed to the accumulation of mtDNA damage.
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