Goulding Richie P, Charlton Braeden T, Breedveld Ellen A, van der Laan Matthijs, Strating Anne R, Noort Wendy, Kolodyazhna Aryna, Appelman Brent, van Vugt Michèle, Grootemaat Anita E, van der Wel Nicole N, de Koning Jos J, Bloemers Frank W, Wüst Rob C I
Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Center for Experimental and Molecular Medicine, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
Aging Cell. 2025 Feb;24(2):e14386. doi: 10.1111/acel.14386. Epub 2024 Dec 4.
Ageing substantially impairs skeletal muscle metabolic and physical function. Skeletal muscle mitochondrial health is also impaired with ageing, but the role of skeletal muscle mitochondrial fragmentation in age-related functional decline remains imprecisely characterized. Here, using a cross-sectional study design, we performed a detailed comparison of skeletal muscle mitochondrial characteristics in relation to in vivo markers of exercise capacity between young and middle-aged individuals. Despite similar overall oxidative phosphorylation capacity (young: 99 ± 17 vs. middle-aged: 99 ± 27 pmol O.s.mg, p = 0.95) and intermyofibrillar mitochondrial density (young: 5.86 ± 0.57 vs. middle-aged: 5.68 ± 1.48%, p = 0.25), older participants displayed a more fragmented intermyofibrillar mitochondrial network (young: 1.15 ± 0.17 vs. middle-aged: 1.55 ± 0.15 A.U., p < 0.0001), a lower mitochondrial cristae density (young: 23.40 ± 7.12 vs. middle-aged: 13.55 ± 4.10%, p = 0.002) and a reduced subsarcolemmal mitochondrial density (young: 22.39 ± 6.50 vs. middle-aged: 13.92 ± 4.95%, p = 0.005). Linear regression analysis showed that 87% of the variance associated with maximal oxygen uptake could be explained by skeletal muscle mitochondrial fragmentation and cristae density alone, whereas subsarcolemmal mitochondrial density was positively associated with the capacity for oxygen extraction during exercise. Intramuscular lipid accumulation was positively associated with mitochondrial fragmentation and negatively associated with cristae density. Collectively, our work highlights the critical role of skeletal muscle mitochondria in age-associated declines in physical function.
衰老会严重损害骨骼肌的代谢和生理功能。骨骼肌线粒体健康也会随着衰老而受损，但骨骼肌线粒体碎片化在与年龄相关的功能衰退中的作用仍未得到精确描述。在这里，我们采用横断面研究设计，对年轻和中年个体的骨骼肌线粒体特征与运动能力的体内标志物进行了详细比较。尽管总体氧化磷酸化能力相似（年轻组：99±17 vs.中年组：99±27 pmol O.s.mg，p = 0.95）以及肌原纤维间线粒体密度相似（年轻组：5.86±0.57 vs.中年组：5.68±1.48%，p = 0.25），但老年参与者的肌原纤维间线粒体网络更加碎片化（年轻组：1.15±0.17 vs.中年组：1.55±0.15 A.U.，p < 0.0001），线粒体嵴密度更低（年轻组：23.40±7.12 vs.中年组：13.55±4.10%，p = 0.002），肌膜下线粒体密度降低（年轻组：22.39±6.50 vs.中年组：13.92±4.95%，p = 0.005）。线性回归分析表明，与最大摄氧量相关的87%的方差仅可由骨骼肌线粒体碎片化和嵴密度解释，而肌膜下线粒体密度与运动期间的氧摄取能力呈正相关。肌肉内脂质积累与线粒体碎片化呈正相关，与嵴密度呈负相关。总的来说，我们的工作突出了骨骼肌线粒体在与年龄相关的身体功能衰退中的关键作用。
