Received November 6, 2006
Revised November 28, 2006
Accepted after revision December 13, 2006
Human, Environmental & Exercise [250]
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MITOCHONDRIAL FUNCTION, FIBER TYPES AND AGING: NEW INSIGHTS
FROM HUMAN MUSCLE IN VIVO
Kevin Conley 1*,
Catherine Amara 1,
Sharon Jubrias 1,
David Marcinek 1
1 University of Washington
* To whom correspondence should be addressed. E-mail: kconley{at}u.washington.edu.
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Abstract |
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Mitochondrial changes are at the heart of a wide range of maladies including diabetes, neurodegeneration and aging-related dysfunctions. Here we show innovative optical and
magnetic resonance spectroscopic methods that non-invasively measure key mitochondrial fluxes, ATP synthesis and O2 uptake, to permit determining mitochondrial coupling efficiency in vivo (ATP/O2 or P/O). Three new insights result. First, mitochondrial coupling can be measured
in vivo with the rigor of a biochemical determination and provide a gold standard to define wellcoupled mitochondria (P/O~2.5). Second, mitochondrial coupling differs substantially among muscles from values reflective of well-coupled oxidative phosphorylation in a hand muscle
(P/O=2.7) to mild uncoupling in a leg muscle (P/O=2.0). Third, these coupling differences have important impact on cell aging. Substantial uncoupling and loss of cellular [ATP] indicative of mitochondrial dysfunction with age was found in the hand muscle. In contrast, stable
mitochondrial function was found in the leg muscle in support of the notion that mild uncoupling is protective against mitochondrial damage with age. Greater mitochondrial dysfunction is evident in muscles with higher type II muscle fiber content, which may be at the root of the preferential loss of type II fibers found in the elderly. These results are the first demonstration that mitochondrial function and the tempo of aging varies among human muscles in the same individual. Thus technical advances in combination with the range of mitochondrial properties available in human muscles provide an ideal system for studying mitochondrial function in normal tissue and the link between mitochondrial defects and cell pathology in disease.
Key Words:
Ageing, Mitochondria, Skeletal muscle
