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. 2009 Mar;11(3):147-52.
doi: 10.1097/GIM.0b013e31819307a2.

Mitochondrial DNA deletion and sarcopenia

Vallabh O Shah  1 , John Scariano, Debra Waters, Clifford Qualls, Marilee Morgan, Gavin Pickett, Chuck Gasparovic, Karol Dokladny, Pope Moseley, Dominic S C Raj
Affiliations

Mitochondrial DNA deletion and sarcopenia

Vallabh O Shah et al. Genet Med. 2009 Mar.

Abstract

Purpose: 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).

Conclusion: 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.

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Figures

Figure 1
Figure 1
Correlation between total cumulative mtDNA deletion and lean body mass (LBM)
Figure 2
Figure 2
Distribution of mitochondrial DNA deletions among the study participants including both normal lean and sarcopenic subjects.
See this image and copyright information in PMC

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