Mitochondrial DNA Heteroplasmy Associations With Neurosensory and Mobility Function in Elderly Adults.
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.
California Pacific Medical Center Research Institute, San Francisco. gtranah@sfcc-cpmc.net.
Gregory J
GJ
Tranah
Department of Psychiatry, Department of Neurology and Department of Epidemiology, University of California San Francisco and the San Francisco VA Medical Center.
Kristine
K
Yaffe
L.A. Eye Center and Clinic, Los Angeles, California.
Shana M
SM
Katzman
BioNano Genomics, Inc., San Diego, California.
Ernest T
ET
Lam
Department of Anesthesia and Perioperative Care, University of California San Francisco. Institute for Human Genetics, University of California San Francisco.
Ludmila
L
Pawlikowska
Institute for Human Genetics, University of California San Francisco.
Pui-Yan
PY
Kwok
J. Craig Venter Institute and the University of California, San Diego.
Nicholas J
NJ
Schork
Department of Aging and Geriatric Research, University of Florida, Gainesville.
Todd M
TM
Manini
Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Stephen
S
Kritchevsky
Department of Preventive Medicine, The University of Tennessee Health Science Center, Memphis.
Fridtjof
F
Thomas
Department of Epidemiology, University of Pittsburgh, Pennsylvania.
Anne B
AB
Newman
Intramural Research Program, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland.
Tamara B
TB
Harris
Jules Stein Eye Institute and UCLA Department of Ophthalmology, Los Angeles, California.
Anne L
AL
Coleman
Jules Stein Eye Institute and UCLA Department of Ophthalmology, Los Angeles, California.
Michael B
MB
Gorin
Department of Epidemiology and Biostatistics, SUNY Downstate Medical Center, Brooklyn, New York.
Elizabeth P
EP
Helzner
California Pacific Medical Center Research Institute, San Francisco.
Michael C
MC
Rowbotham
California Pacific Medical Center Research Institute, San Francisco.
Warren S
WS
Browner
California Pacific Medical Center Research Institute, San Francisco.
Steven R
SR
Cummings
D000368:Aged; D003072:Cognition Disorders / Q000235:genetics*; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics*; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics*; D051346:Mobility Limitation; D012678:Sensation Disorders / Q000235:genetics*
D004272:DNA, Mitochondrial
Cognition; Hearing; Heteroplasmy; Mitochondrial DNA; Mobility.; Vision