Mitochondrial DNA deletion and sarcopenia.
OBJECTIVE
Accumulation of mitochondrial DNA deletions and the resultant impaired oxidative phosphorylation may play a pathogenic role in the mediation of age-related sarcopenia.


METHODS
Twenty four participants of the New Mexico Aging Process Study were classified as normal lean (n = 15) or sarcopenic (n = 9) based on body composition determined by Dual Energy x-ray Absorptiometry. Complex I and Complex IV activities were measured in the skeletal muscle samples obtained from gastrocnemius muscle. A two-stage nested polymerase chain reaction strategy was used to identify the mitochondrial DNA deletions in the entire mitochondrial genome in the skeletal muscle samples.


RESULTS
Although Complex I activity was not significantly different (5.5 +/- 0.9 vs. 4.6 +/- 0.7 mU/mg protein, P > 0.05), Complex IV activity was higher in sarcopenic subjects (1.4 +/- 0.3 vs. 1.0 +/- 0.1 mU/mg protein, P < 0.05). Mitochondrial DNA deletions were mostly located in the region of Complex I and spanned from nicotinamide adenine dinucleotide dehydrogenase 1 to nicotinamide adenine dinucleotide dehydrogenase 6. Deletions in the 8,577-10,407 bp and 10,233-11,249 bp regions were associated with a significant decrease in Complex I activity (P < 0.05 and P = 0.02, respectively). Total cumulative deletion, defined as the sum of individual length of deletions in a subject, was comparable in subjects with and without sarcopenia (1760 +/- 726 vs. 1782 +/- 888 bp, P > 0.05). The magnitude of mitochondrial DNA deletion, however, correlated positively with lean body mass (r = 0.43, P < 0.05).


CONCLUSIONS
Thus, mitochondrial DNA deletions are common in elderly subjects and are negatively related to Complex I activity. The positive association between mitochondrial DNA deletions and lean body mass needs to be confirmed by studies in a larger study population.
Department of Biochemistry, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
Vallabh O
VO
Shah
John
J
Scariano
Debra
D
Waters
Clifford
C
Qualls
Marilee
M
Morgan
Gavin
G
Pickett
Chuck
C
Gasparovic
Karol
K
Dokladny
Pope
P
Moseley
Dominic S C
DS
Raj
D015502:Absorptiometry, Photon; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005260:Female; D054629:Genome, Mitochondrial / Q000235:genetics; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology; D009516:New Mexico; D016133:Polymerase Chain Reaction / Q000379:methods; D017384:Sequence Deletion
D004272:DNA, Mitochondrial; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I