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J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1418-24. doi: 10.1093/gerona/glv097. Epub 2015 Aug 31.

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

Author information

1
California Pacific Medical Center Research Institute, San Francisco. gtranah@sfcc-cpmc.net.
2
Department of Psychiatry, Department of Neurology and Department of Epidemiology, University of California San Francisco and the San Francisco VA Medical Center.
3
L.A. Eye Center and Clinic, Los Angeles, California.
4
BioNano Genomics, Inc., San Diego, California.
5
Department of Anesthesia and Perioperative Care, University of California San Francisco. Institute for Human Genetics, University of California San Francisco.
6
Institute for Human Genetics, University of California San Francisco.
7
J. Craig Venter Institute and the University of California, San Diego.
8
Department of Aging and Geriatric Research, University of Florida, Gainesville.
9
Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina.
10
Department of Preventive Medicine, The University of Tennessee Health Science Center, Memphis.
11
Department of Epidemiology, University of Pittsburgh, Pennsylvania.
12
Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland.
13
Jules Stein Eye Institute and UCLA Department of Ophthalmology, Los Angeles, California.
14
Department of Epidemiology and Biostatistics, SUNY Downstate Medical Center, Brooklyn, New York.
15
California Pacific Medical Center Research Institute, San Francisco.

Abstract

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.

KEYWORDS:

Cognition; Hearing; Heteroplasmy; Mitochondrial DNA; Mobility.; Vision

PMID:
26328603
PMCID:
PMC4612388
DOI:
10.1093/gerona/glv097
[Indexed for MEDLINE]
Free PMC Article

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