Mau Theresa, Blackwell Terri L, Cawthon Peggy M, Molina Anthony J A, Coen Paul M, Distefano Giovanna, Kramer Philip A, Ramos Sofhia V, Forman Daniel E, Goodpaster Bret H, Toledo Frederico G S, Duchowny Kate A, Sparks Lauren M, Newman Anne B, Kritchevsky Stephen B, Cummings Steven R
San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, California.
Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
medRxiv. 2023 Nov 7:2023.11.06.23298175. doi: 10.1101/2023.11.06.23298175.
The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.
The Study of Muscle, Mobility and Aging (SOMMA) assessed muscle mitochondrial energetics in 764 older adults (mean age =76.4, 56.5% women, 85.9% non-Hispanic white) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95%CI]) for the likelihood of greater multimorbidity (four levels: 0 conditions, N=332; 1 condition, N=299; 2 conditions, N=98; or 3+ conditions, N=35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions.
Lower oxidative phosphorylation supported by fatty acids and/or complex-I and -II linked carbohydrates (e.g., Max OXPHOS) was associated with a greater multimorbidity index score (POR=1.32[1.13,1.54]) and separately with diabetes mellitus (OR=1.62[1.26,2.09]), depressive symptoms (OR=1.45[1.04,2.00]) and possibly chronic kidney disease (OR=1.57[0.98,2.52]) but not significantly with other conditions (e.g., cardiac arrhythmia, chronic obstructive pulmonary disease).
Lower muscle mitochondrial bioenergetic capacities was associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and is more strongly related to some conditions than others.
老年科学假说认为，衰老的生物学过程会导致许多与年龄相关的缺陷，包括多种慢性疾病的积累。尽管肌肉线粒体生物能量能力的下降只是线粒体功能的一个方面，但它可能导致对多种疾病易感性的增加。
肌肉、运动与衰老研究（SOMMA）通过对透化肌纤维进行高分辨率呼吸测定，评估了764名老年人（平均年龄=76.4岁，56.5%为女性，85.9%为非西班牙裔白人）的肌肉线粒体能量学。我们根据11种疾病的指数，计算了肌肉线粒体能量参数每降低一个标准差时，多发病率更高（四个级别：0种疾病，N=332；1种疾病，N=299；2种疾病，N=98；或3种及以上疾病，N=35）的可能性的比例优势比（POR[95%置信区间]）。疾病的分布情况使得我们能够测试最大肌肉能量学与某些个体疾病之间的关联。
脂肪酸和/或与复合体I和II相关的碳水化合物所支持的较低氧化磷酸化（例如，最大氧化磷酸化）与更高的多发病率指数得分相关（POR=1.32[1.13,1.54]），并分别与糖尿病（OR=1.62[1.26,2.09]）、抑郁症状（OR=1.45[1.04,2.00]）以及可能的慢性肾病（OR=1.57[0.98,2.52]）相关，但与其他疾病（例如心律失常、慢性阻塞性肺疾病）无显著关联。
较低的肌肉线粒体生物能量能力与更差的综合多发病率指数得分相关。我们的结果表明，肌肉线粒体能量学的下降可能导致更大的全球疾病负担，并且与某些疾病的关联比其他疾病更强。
