Aberrant Mitochondrial Homeostasis in the Skeletal Muscle of Sedentary Older Adults

Abstract

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; ♀ = ♂). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

Mitochondrial biogenesis and angiogenesis in skeletal muscle of the elderly

“…In contrast to previously reported mitochondrial dysfunction in elderly [28,39,53], the present findings are in line with previous studies showing that mitochondria from skeletal muscle of elderly subjects are well functioning [44,47]. The finding that both the endurance trained and untrained elderly subjects in the present study had ~2 fold lower αKG-DH/CS activity ratio than previously observed in young subjects [2], is apparently due to a higher CS activity rather than a…”

“…However little is known about the ability to prevent the potential age-associated decrease in oxidative enzyme capacity with exercise training, although previous observations indicate that this might be possible [47]. Thus, previous studies reported that elderly orienteer runners had SDH, CS and 3-hydroxy-acyl-CoA-dehydrogenase (HAD) activities at the same level as endurance trained young subjects [9,48].…”

“…It may be speculated that this upregulation of CS activity is caused by an increased requirement of biosynthesis of triglycerides from citrate in elderly subjects for a yet unknown reason. A potential impairment of mitochondrial function in elderly and old subjects may be related to their training status, as the elderly [44] and old [47] subjects with well functioning mitochondria in previous studies were endurance trained at different levels, while the elderly with impaired mitochondrial function were sedentary [39]. In addition, it is likely that mitochondrial dysfunction may be more pronounced after the age of ~75 and only slightly detectable at a younger age, as it has been suggested for the hypertrophic response to resistance exercise training [52].…”

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

“…Mitochondrial abnormalities and mtDNA mutagenesis are well-established intrinsic instigators that drive multisystem degeneration, stress intolerance, and energy deficits during aging in humans (3), monkeys (4), and rodents (5). Reduced mitochondrial quality and content in multiple tissues is also implicated in several aging-associated conditions, including cancer, obesity, cardiovascular diseases, hypertension, type 2 diabetes, osteoporosis, and dementia, as well as in the pathogenesis of neurometabolic syndromes, psychiatric disorders, end-stage renal disease, and mitochondrial cytopathies (6)(7)(8)(9)(10). Current treatment strategies for conditions associated with mitochondrial dysfunction address the secondary symptoms but not the deficiency itself (11).…”

The Emerging Role of p53 in Exercise Metabolism

“…From a functional perspective, the study of the regulation of mitochondrial biogenesis has obvious implications for both human health and performance. Impaired mitochondrial function is associated with the pathology of many metabolic disorders such as insulin resistance and type 2 diabetes [2], obesity [3], ageing [4] and cancer [5]. In relation to exercise performance, the increased mitochondrial content that accompanies exercise training ensures that exercise in the trained state induces less disturbance to metabolic homeostasis for a given exercise intensity.…”