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.
journal_name
Proc Natl Acad Sci U S Aauthors
Amara CE,Shankland EG,Jubrias SA,Marcinek DJ,Kushmerick MJ,Conley KEdoi
10.1073/pnas.0610131104subject
Has Abstractpub_date
2007-01-16 00:00:00pages
1057-62issue
3eissn
0027-8424issn
1091-6490pii
0610131104journal_volume
104pub_type
杂志文章abstract::Natural selection does not necessarily favor maximal reproduction because reproduction imposes fitness costs, reducing parental survival, and offspring quality. Here, we show that parents in a preindustrial population in North America incurred fitness costs from reproduction, and women incurred greater costs than men....
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