Sonjak 2019 J Gerontol A Biol Sci Med Sci
|Sonjak V, Jacob KJ, Spendiff S, Vuda M, Perez A, Miguez K, Minozzo FC, Spake C, Morais JA, Hepple RT (2019) Reduced mitochondrial content, elevated ROS, and modulation by denervation in skeletal muscle of pre-frail/frail elderly women. J Gerontol A Biol Sci Med Sci [Epub ahead of print].|
Abstract: Denervation and mitochondrial impairment are implicated in age-related skeletal muscle atrophy, and may play a role in physical frailty. We recently showed that denervation modulates muscle mitochondrial function in octogenarian men, but this has not been examined in elderly women. On this basis we tested the hypothesis that denervation plays a modulating role in mitochondrial impairment in skeletal muscle from prefrail/frail elderly (FE) women. Mitochondrial respiratory capacity and reactive oxygen species (ROS) emission were examined in permeabilized myofibers obtained from Vastus lateralis muscle biopsies from FE and young inactive (YI) women. Muscle respiratory capacity was reduced in proportion to a reduction in a mitochondrial marker protein in FE, and mitochondrial ROS emission was elevated in FE versus YI group. Consistent with a significant accumulation of neural cell adhesion molecule positive muscle fibers in FE (indicative of denervation), a 50% reduction in ROS production after pharmacologically inhibiting the denervation-mediated ROS response in FE women suggests a significant modulation of mitochondrial function by denervation. In conclusion, our data support the hypothesis that denervation plays a modulating role on skeletal muscle mitochondrial function in FE women, suggesting therapeutic strategies in advanced age should focus on the causes and treatment of denervation.
© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
Labels: MiParea: Respiration Pathology: Aging;senescence
Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS Pathway: N, CIV, NS, ROX HRR: Oxygraph-2k