Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo
Year: 2007
Type: article
Study design: Observational Study
Abstract: Faster aging is predicted in more active tissues and animals because of greater reactive oxygen species generation. Yet age-related cell loss is greater in less active cell types, such as type II muscle fibers. Mitochondrial uncoupling has been proposed as a mechanism that reduces reactive oxygen species production and could account for this paradox between longevity and activity. We distinguished these hypotheses by using innovative optical and magnetic resonance spectroscopic methods applied to noninvasively measured ATP synthesis and O(2) uptake in vivo in human muscle. Here we show that mitochondrial function is unchanged with age in mildly uncoupled tibialis anterior muscle (75% type I) despite a high respiratory rate in adults. In contrast, substantial uncoupling and loss of cellular [ATP] indicative of mitochondrial dysfunction with age was found in the lower respiring and well coupled first dorsal interosseus (43-50% type II) of the same subjects. These results reject respiration rate as the sole factor impacting the tempo of cellular aging. Instead, they support mild uncoupling as a mechanism protecting mitochondrial function and contributing to the paradoxical longevity of the most active muscle fibers.
Institution: University of Washington Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1359795617, Mitochondrial function, oxidative damage, and aging, G2882306852, Genetic Approaches to Aging, RESPIRATION AND GLYCOLYSIS--INTEGRATION IN ACTIVE MUSCLE, MR & Optical Diagnosis of Mitochondrial Metabolism and Dysfunction, Mitochondrial Dysfunction in Aged Muscle, CELLULAR RESPIRATION IN MUSCLE ENERGY BALANCE, G9000247674
OpenAlex ID: W2129876483