The global population is aging rapidly, particularly in high-income countries, leading to a significant increase in age-related health issues and healthcare costs. Sarcopenia, the age-related loss of muscle mass and function, is a major concern, contributing to mobility limitations, falls, frailty, and metabolic impairments. Mitochondrial dysfunction in skeletal muscle is another hallmark of aging, and preclinical studies suggest it may play a crucial role in sarcopenia. However, the exact relationship between age-related mitochondrial decline, physical inactivity, and the deterioration of muscle health remains unclear. This study aimed to clarify these relationships by comparing mitochondrial function and muscle health in young and older adults with varying levels of physical activity, including those with normal activity levels, those who are exercise-trained, and those who are physically impaired. The study sought to determine if mitochondrial function decreases with age even in individuals maintaining a healthy level of physical activity, and it also investigated whether regular exercise training can mitigate the effects of aging on mitochondrial function and muscle health.

Previous research has demonstrated a decline in mitochondrial respiratory activity in skeletal muscle with advancing age, impacting muscle function. Studies have shown correlations between mitochondrial master regulator PGC-1α protein levels and walking speed in older adults. Preclinical research in animals further supports the link between reduced mitochondrial function and muscle health decline, with transgenic mice lacking SOD1 exhibiting accelerated sarcopenia. However, human studies on this topic are limited and often focus solely on either muscle function decline or mitochondrial alterations. Furthermore, the role of age-related physical inactivity in mitochondrial dysfunction is not fully understood, with decreased physical activity negatively affecting mitochondrial capacity, while exercise training stimulates mitochondrial biogenesis. This existing literature creates a knowledge gap regarding the relative contributions of chronological age and physical inactivity to age-related decline in mitochondrial function and muscle health.

This cross-sectional study involved 59 participants: 17 young adults (20-30 years) and 42 older adults (65-80 years). Older adults were categorized into three groups: those with normal physical activity (O), trained older adults (TO), and physically impaired older adults (IO). Participants underwent a comprehensive assessment of muscle health, including body composition analysis (BodPod), physical function tests (6-minute walk test, maximal aerobic capacity test, isokinetic muscle strength assessment, gait stability assessments using a treadmill system with perturbations), insulin sensitivity measurement (hyperinsulinemic-euglycemic clamp), resting energy expenditure measurement, and submaximal exercise tests. Skeletal muscle biopsies were performed to assess mitochondrial capacity using high-resolution respirometry (Oroboros). In vivo mitochondrial function was measured with 31P-magnetic resonance spectroscopy (31P-MRS). Mitochondrial protein expression levels were also determined using Western Blot analysis. Habitual physical activity was measured using accelerometry (ActivPAL). Statistical analyses included t-tests, ANOVA, and correlation analyses.

Compared to young adults with similar daily step counts (~10,000), older adults with normal physical activity levels showed significant reductions in mitochondrial capacity (both ex vivo and in vivo), maximal aerobic capacity (VO2max), exercise efficiency, gait stability, muscle strength, and insulin sensitivity. However, exercise-trained older adults demonstrated significantly higher mitochondrial function (ex vivo and in vivo), improved muscle strength, endurance, and exercise efficiency, and higher whole-body insulin sensitivity compared to older adults with normal physical activity. Physically impaired older adults showed the poorest performance across all measures, although limited sample size warrants cautious interpretation of these findings. Correlations were observed between various measures of mitochondrial function (ex vivo respiration, in vivo PCr recovery, and VO2max), exercise efficiency, and physical function parameters (6MWT, chair-stand test, gait variability).

This study demonstrates that age-related decline in skeletal muscle mitochondrial function occurs even in older adults who maintain a healthy level of daily physical activity. The significant improvements observed in exercise-trained older adults highlight the potential of regular exercise to mitigate these age-related declines and maintain muscle health. The strong correlations between mitochondrial function, exercise efficiency, and various measures of physical function support the importance of mitochondrial function in maintaining muscle health and physical performance in older adults. The lack of significant differences in mitochondrial capacity between normally active and physically impaired older adults, despite differences in muscle function, suggests that factors beyond mitochondrial function may contribute to physical impairment in this group.

This study provides strong evidence that aging is associated with reduced mitochondrial capacity and impaired muscle health, even in active older adults. However, the impact of aging can be significantly mitigated by regular exercise training, leading to substantial improvements in both mitochondrial function and overall muscle health. The findings underscore the importance of exercise in maintaining healthy aging and preserving physical function. Future research could focus on identifying specific exercise interventions to maximize the benefits on mitochondrial function and muscle health and investigate potential gender-specific differences.

The cross-sectional design limits causal inferences. The relatively small sample size, especially in the physically impaired older adult group, affects the statistical power and generalizability of the findings. The study focuses on a specific age range and does not fully encompass the entire spectrum of aging. The measurements of habitual physical activity may not fully capture the intensity and diversity of activities.