Mitochondrial DNA sequence variation is associated with free-living activity energy expenditure in the elderly
| Autor: | Tranah, Gregory J, Lam, Ernest T, Katzman, Shana M, Nalls, Michael A, Zhao, Yiqiang, Evans, Daniel S, Yokoyama, Jennifer S, Pawlikowska, Ludmila, Kwok, Pui-Yan, Mooney, Sean, Kritchevsky, Stephen, Goodpaster, Bret H, Newman, Anne B, Harris, Tamara B, Manini, Todd M, Cummings, Steven R, Health, Aging and Body Composition Study |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Aging mtDNA DNA Biological Sciences Metabolic rate Oxidative Phosphorylation Mitochondrial Mitochondria Cohort Studies Health Physical Sciences Activities of Daily Living Genetics Humans Female Energy expenditure Generic health relevance Prospective Studies DNA sequencing Aging and Body Composition Study Energy Metabolism Sequence Analysis Metabolic and endocrine Aged |
| Zdroj: | Biochimica et biophysica acta, vol 1817, iss 9 |
| Popis: | The decline in activity energy expenditure underlies a range of age-associated pathological conditions, neuromuscular and neurological impairments, disability, and mortality. The majority (90%) of the energy needs of the human body are met by mitochondrial oxidative phosphorylation (OXPHOS). OXPHOS is dependent on the coordinated expression and interaction of genes encoded in the nuclear and mitochondrial genomes. We examined the role of mitochondrial genomic variation in free-living activity energy expenditure (AEE) and physical activity levels (PAL) by sequencing the entire (~16.5 kilobases) mtDNA from 138 Health, Aging, and Body Composition Study participants. Among the common mtDNA variants, the hypervariable region 2 m.185G>A variant was significantly associated with AEE (p=0.001) and PAL (p=0.0005) after adjustment for multiple comparisons. Several unique nonsynonymous variants were identified in the extremes of AEE with some occurring at highly conserved sites predicted to affect protein structure and function. Of interest is the p.T194M, CytB substitution in the lower extreme of AEE occurring at a residue in the Qi site of complex III. Among participants with low activity levels, the burden of singleton variants was 30% higher across the entire mtDNA and OXPHOS complex I when compared to those having moderate to high activity levels. A significant pooled variant association across the hypervariable 2 region was observed for AEE and PAL. These results suggest that mtDNA variation is associated with free-living AEE in older persons and may generate new hypotheses by which specific mtDNA complexes, genes, and variants may contribute to the maintenance of activity levels in late life. |
| Databáze: | OpenAIRE |
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