A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys

Aging Cell

Thomas D. Pugh³  Matthew W. Conklin⁵  Trent D. Evans³  Michael A. Polewski³  Hannah J. Barbian³  Rachelle Pass³  Bradley D. Anderson³  Ricki J. Colman¹  Kevin W. Eliceiri⁵  Patricia J. Keely²  Richard Weindruch³  T. Mark Beasley⁴ 

[1] National Primate Research Center, University of Wisconsin, Madison, WI, USA;Department of Cell and Regenerative Biology, University of Wisconsin, Madison, WI, USA;Department of Medicine, University of Wisconsin, Madison, WI, USA;Department of Biostatistics, University of Alabama, Birmingham, AL, USA;Laboratory for Optical and Computational Instrumentation, University of Wisconsin, Madison, WI, USA

关键词: aging;    metabolism;    mitochondria;    NAD;    PGC‐1α;    skeletal muscle;    rhesus monkeys;   

DOI  :  10.1111/acel.12091

来源: Wiley

【 摘 要 】

Summary

Age-associated skeletal muscle mass loss curtails quality of life and may contribute to defects in metabolic homeostasis in older persons. The onset of sarcopenia occurs in middle age in rhesus macaques although the trigger has yet to be identified. Here, we show that a shift in metabolism occurs in advance of the onset of sarcopenia in rhesus vastus lateralis. Multiphoton laser-scanning microscopy detects a shift in the kinetics of photon emission from autofluorescent metabolic cofactors NADH and FAD. Lifetime of both fluorophores is shortened at mid-age, and this is observed in both free and bound constituent pools. Levels of FAD and free NADH are increased and the NAD/NADH redox ratio is lower. Concomitant with this, expression of fiber-type myosin isoforms is altered resulting in a shift in fiber-type distribution, activity of cytochrome c oxidase involved in mitochondrial oxidative phosphorylation is significantly lower, and the subcellular organization of mitochondria in oxidative fibers is compromised. A regulatory switch involving the transcriptional coactivator PGC-1α directs metabolic fuel utilization and governs the expression of structural proteins. Age did not significantly impact total levels of PGC-1α; however, its subcellular localization was disrupted, suggesting that PGC-1α activities may be compromised. Consistent with this, intracellular lipid storage is altered and there is shift to larger lipid droplet size that likely reflects a decline in lipid turnover or a loss in efficiency of lipid metabolism. We suggest that changes in energy metabolism contribute directly to skeletal muscle aging in rhesus monkeys.

【 授权许可】

Unknown   
© 2013 John Wiley & Sons Ltd and the Anatomical Society