Resistance Training Rebuilt Aging Mitochondria in 10 Weeks

Aging is characterized by progressive decline in skeletal muscle health, associated with decreased quality of life and increased mortality. Besides decreases in muscle mass and strength—termed sarcopenia—an age-related reduction in skeletal muscle oxidative capacity and cardiorespiratory fitness has been reported. However, researchers have postulated that decreased physical activity and fitness, and not aging per se, might be the cause of reduced skeletal muscle mitochondrial function.

Mitochondria have been considered to play an important role in sarcopenia and reduced skeletal muscle function. In skeletal muscle, mitochondria exist as a highly dynamic network that responds to the energy demands of the cell. Mitochondria undergo constant remodeling through biogenesis (generation of new mitochondria), fusion (joining), fission (splitting), and mitophagy (degradation of dysfunctional portions). Adequate remodeling processes are essential for maintaining functional mitochondria.

A study published in Physiological Reports investigated the acute and chronic effects of resistance training on markers of mitochondrial content and remodeling in older, untrained individuals. Sixteen older adults (age 59 plus or minus 4 years, 70% female) completed 10 weeks of full-body resistance training performed twice weekly. The findings demonstrated that chronic resistance training dramatically increased mitochondrial protein content and improved mitochondrial dynamics.

The Protocol and Training Adaptations

The training program was supervised and consisted of a whole-body workout performed twice weekly for 10 weeks. During each session, participants performed three sets of 10-12 repetitions of leg press, leg extensions, leg curls, barbell bench press, and cable pull downs, with at least 1 minute rest between sets. At the end of each set, participants rated difficulty (0 equals easy, 10 equals hard). The goal was to ensure participants gauged sets between 7 and 9 rating.

Participants were older adults (ages 55-80) with no structured resistance training over the past year, body mass index less than 35, stable weight for the past 6 months, and no cardio-metabolic diseases. The cohort had an average body mass index of 31.7 with 39.3% body fat at baseline.

VL muscle thickness increased from 1.88 cm to 2.02 cm with training. Knee extensor peak torque increased from 115 to 127 Newton meters. Both increases were significant.

All Five Electron Transport Chain Complexes Increased

Acute resistance training (24 hours following the first session) did not significantly affect skeletal muscle protein levels of any electron transport chain complexes. However, after 10 weeks, all five complexes had increased protein levels compared to baseline. Complex I increased 180%, Complex II increased 39%, Complex III increased 89%, Complex IV increased 43%, and Complex V increased 78%.

These complexes are responsible for oxidative phosphorylation—the process that produces ATP, the cellular energy currency. Age-related decline in these proteins contributes to reduced muscle oxidative capacity and cardiorespiratory fitness in older adults.

Previous studies have found increased mitochondrial content in older subjects in response to resistance training. However, no significant changes or even decreases in mitochondrial function have also been reported. Training protocols that elicit greater metabolic demands seem more beneficial to mitochondrial adaptations. Furthermore, physical activity levels and fitness are possible confounding factors. A decline in physical activity—and not aging per se—might cause decreased mitochondrial content or function.

The resistance training protocol in this study was sufficient stimulus to elicit oxidative adaptations because participants were poorly conditioned prior to training. Resistance training might only be beneficial to poorly conditioned individuals, acting to restore a healthy mitochondrial status. This suggests greatest mitochondrial benefits may occur in those who have experienced the most decline due to inactivity.

Increased Fusion Counteracts Age-Related Fragmentation

Mfn1 and Mfn2 protein levels did not change following acute resistance training but increased following chronic training. Mfn1 increased 90% and Mfn2 increased 110%. Opa1 protein levels increased following both acute (115%) and chronic training (261%). These proteins mediate fusion of mitochondrial membranes.

Drp1 protein levels did not change following acute training but increased following chronic training (134%). Fis1 protein levels showed no changes. These proteins are involved in mitochondrial fission.

The more robust increase in fusion markers compared to fission markers points to a scenario of increased mitochondrial fusion. Studies have shown that proper mitochondrial dynamics are impaired during aging. Age-related increase in fission leads to a fragmented mitochondrial network, linked to mitochondrial dysfunction. The increased fusion observed with training could be a positive adaptation to counteract age-related increased fission.

Increased mitochondrial damage is reported with aging and fusion could have a role in mixing contents of two mitochondria and possibly diluting damaged material. The data support that resistance training positively affects mitochondrial fusion markers, and this adaptation may have led to enhanced mitochondrial function.

Biogenesis and Mitophagy Markers Remained Stable

Despite clear roles of PGC-1α, NRF1, and TFAM on mitochondrial biogenesis, the only significant change detected was acute increase in NRF1 protein levels (98%). No significant differences were detected for PGC-1α or TFAM following acute or chronic training.

Similar contradictory results showing increased mitochondrial content but no change in biogenesis markers have been reported in response to training. The contradictory results might be related to timing of biopsy. Furthermore, researchers have recently shown that other proteins, such as PPARβ, may also be important in regulating mitochondrial biogenesis.

Results showed no change in Pink1 and Parkin protein levels in response to acute or chronic training, which is not surprising considering that fission precedes mitophagy and a more robust increase in fusion markers compared to fission markers was detected. These results do not necessarily mean unaltered mitophagy. Pink1 and Parkin are subjected to phosphorylation events that impact their activity, and these were not analyzed. Mitophagy could also occur through Pink1 Parkin-independent pathways.

The Clinical Significance

Mitochondrial dysfunction is intricately linked with muscle aging. The causes of sarcopenia and reduced skeletal muscle function are multifactorial, but mitochondria play an important role. Age-related decline in mitochondrial function contributes to reduced muscle mass and strength, decreased oxidative capacity, and lower cardiorespiratory fitness. These declines are associated with decreased quality of life and increased mortality in elderly populations.

The key insight is that decreased physical activity and fitness—and not aging per se—might be the cause of reduced skeletal muscle mitochondrial function. This is empowering. It suggests that mitochondrial decline is not inevitable, but rather a consequence of inactivity that can be reversed.

Resistance training has been well recognized as effective for increasing muscle hypertrophy and strength. This study adds evidence that resistance training is also a viable approach to improve proteins involved in oxidative phosphorylation and mitochondrial dynamics. These mitochondrial adaptations could contribute to preservation of muscle function, maintenance of metabolic health, and prevention of age-related functional decline.

The results suggest that acute response (measured 24 hours after first session) may not be representative of chronic effects, and that repeated bouts are necessary to achieve mitochondrial benefits in older populations. This has practical implications: older adults beginning resistance training should commit to consistent training over weeks to months to realize mitochondrial adaptations.

Study Limitations

Limitations include no control group of younger participants, so changes observed might not be age-specific. Mitochondrial function can differ between males and females, but sample size did not enable such comparisons. Acute responses were determined at single time point (24 hours), so important changes at other time points may have been missed.

Although changes in proteins related to mitochondrial content and dynamics were detected, measures of oxidative phosphorylation were not conducted due to tissue limitations. However, studies have linked increased protein content to observed increased mitochondrial function in response to training.

The Practical Takeaway

Ten weeks of twice-weekly full-body resistance training increased content of electron transport chain proteins and improved mitochondrial dynamics in older, previously untrained adults. All five electron transport chain complexes showed substantial increases, with Complex I increasing 180%. Markers of mitochondrial fusion increased dramatically, with Opa1 increasing 261%.

The increased mitochondrial fusion is particularly significant because it represents a positive adaptation to counteract age-related mitochondrial fragmentation. This could lead to enhanced mitochondrial function, better cellular energy production, and improved muscle health.

Besides known improvements in muscle mass and strength, resistance training is a viable approach to improve proteins involved in oxidative phosphorylation and mitochondrial dynamics. These cellular adaptations may underlie improvements in fatigue resistance, functional capacity, and metabolic health observed with resistance training in older adults.

The implication is clear: resistance training functions as cellular medicine, acting at the mitochondrial level to counteract age-related decline. For poorly conditioned older adults, resistance training may act to restore a healthy mitochondrial status that has been compromised by inactivity. This restoration could contribute to preservation of muscle function, maintenance of independence, and improved quality of life in aging populations.

The prescription is straightforward: full-body resistance training, performed twice weekly, with exercises taken to moderate difficulty (7 to 9 out of 10 rating). This is sufficient to drive meaningful mitochondrial adaptations. The barrier is not complexity, but consistency over time.

Study: Mesquita, P. H. C., Lamb, D. A., Parry, H. A., Moore, J. H., Smith, M. A., Vann, C. G., Osburn, S. C., Fox, C. D., Ruple, B. A., Huggins, K. W., Fruge, A. D., Young, K. C., Kavazis, A. N., & Roberts, M. D. (2020). Acute and chronic effects of resistance training on skeletal muscle markers of mitochondrial remodeling in older adults. Physiological Reports, 8(15), e14526.