Biological mechanisms underlying the aging phenotypes

Authors

• L Ferrucci

Abstract

Muscle mass and muscle strength decline with aging with steeper rates after age 70. Identifying the mechanism for such decline is important for treatment and prevention. In a matched case-control study nested in the Baltimore Longitudinal Study of Aging (BLSA), we found that adiposity was inversely correlated with low muscle quality. Longitudinally, adiposity predicted future accelerated rates of decline in muscle quality. Fat in muscle may cause problems to: 1) mitochondria oxidative phosphorylation; 2) energetic metabolism; 3) architectural organization of muscle fibers. Mitochodrial muscle bioenergetics was assessed as post-exercise recovery rate of phosphocreatine by phosphorus magnetic resonance spectroscopy. Mitochondrial function was independently associated with performance in walking tasks that require speed and endurance. In mediation analyses this association was explained by the negative effect of impaired mitochondrial function on muscle performance. While muscle bioenergetics was not associated with current adiposity, those who had impaired mitochondria energetics had experienced larger weight gain over the previous 20 years. Low muscle quality was associated with higher levels of leucine, isoleucine, tryptophan, serotonin, and methionine, while high muscle quality was associated with lower putrescine and the selected phophatidylcholines. Studies by MRI diffusion tensor analysis and Cryo-Electron Microscopy suggest that aging is associated with less organized and harmonic fibers orientation as well as fractures in the continuity between serial sarcomere chains. Increased adiposity over the life span may lead to impaired mitochondrial function, and eventually reduced ability to incorporate AA to maintain protein homeostasis, which have important consequence on skeletal muscle structure and function.

Scientific Focus Area: Institute, Center, and Scientific Directors

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