A Proteomic View of the Slowing of Muscle Loss with Aging via Physical Exercise

Regular physical exercise acts to slow the characteristic loss of muscle mass and strength that occurs with aging, a condition known as sarcopenia once it reaches the point of frailty. In this, strength training appears to work more effectively than aerobic exercise, but both have their place in the overall picture. In the paper here, researchers report on their assessment of proteomic changes with both aging and exercise. They find that, much as expected, the changes in protein levels that occur with age are largely opposed by the changes in protein levels caused by physical activity.

The decline in muscle strength is one of the most striking phenotypes of aging, which is only partially accounted for by a reduction in muscle mass, suggesting a loss of cellular and molecular integrity of muscle tissue, and/or impairment of neuromuscular control with aging. Low muscle strength is a powerful, independent predictor of slow gait, mobility disability, and early mortality. No interventions are currently available that can prevent or attenuate the decline in muscle strength with aging except exercise, especially resistance training. In spite of this evidence, the percentage of people who regularly exercise is still low and this percentage declines with aging.

It has been suggested that people who have an active lifestyle in daily life have a slower decline of muscle mass and strength with aging. Understanding how physical activity in daily life affects muscle physiology in older persons might help in developing new interventions that, by targeting the same mechanisms triggered by physical activity, could prevent the development of muscle impairment with aging. Numerous studies have investigated the impact of a sedentary lifestyle and low physical activity on health outcomes in both younger and older individuals. Physical inactivity, either long or short-term, negatively affects muscle performance and is associated with diminished aerobic capacity, as well as reduced insulin sensitivity and basal metabolic rate. Furthermore, physical activity alone has been shown to improve and regulate metabolic homeostasis and metabolic efficiency.

Overall, an active lifestyle could be conceptualized as a mixture of aerobic and resistance exercise, but the intermittent, and variable mixture of these activities make it difficult to study. Endurance and resistance training elicit both common and specific metabolic/morphologic adaptations in muscle, some of which are common between tissues. In general, the stress that is induced by exercise challenges energy homeostasis in myocytes, shifting the cellular environment towards an oxidative state. This induces microdamage that stimulates both transcriptional and posttranscriptional responses, which then promotes synthesis of specific proteins that seek to reestablish a different homeostatic equilibrium. Endurance training maximally stimulates mitochondrial biogenesis, enhances aerobic metabolism and fatty acid utilization, and produces change in muscle fiber composition. In contrast, heavy resistance training stimulates the synthesis of contractile proteins, leading to muscle hypertrophy, and increases in maximal contractile force speed and output. Whether an active lifestyle is sufficient to activate the same biological mechanisms triggered by endurance and resistance training is unknown.

In recent years, a handful of studies have examined the protein composition of human muscle cell types and tissues including proteomic differences between old and young muscle, athletes and non-athletes, exercise in extreme conditions, and physical activity and metabolic disorders. These studies have helped to characterize the physiological adaptations of healthy human muscle to different types of exercise. Most of these studies focused on the acute and immediate effects of short bouts of high intensity exercise in either human or mice/rat models, as well as long-term effects of exercise. However, very little research has focused on assessing the association of daily physical activity with the muscle proteome in healthy community-dwelling individuals.

To verify whether an active lifestyle is associated with detectable changes in skeletal muscle and to start to characterize these changes, we performed a quantitative, mass spectrometry-based proteome analysis of muscle specimens from a group of well-characterized healthy individuals with a wide age-range (20-87 years) and who self-reported different levels of physical activity. Independent of age and technical covariates, we found that high levels of physical activity (versus low levels) were associated with an overrepresentation of mitochondrial proteins, tricarboxylic acid (TCA) cycle enzymes, chaperone proteins, and proteins associated with genome maintenance. In contrast, proteins related to the spliceosome and transcription regulation, immune proteins, apoptosis proteins, DNA damage proteins, and senescent proteins were underrepresented in muscle of participants who reported higher physical activity. Differences observed were mostly opposite to those observed with skeletal muscle aging.

Link: https://doi.org/10.3389/fphys.2019.00312


As a layman, active gym goer and outdoor man, I struggle to understand the mTOR pathway in the context of exercise and aging. On one hand exercise, especially resistance exercise is said to activate the mTOR signaling pathway to enhance protein synthesis to build more muscles. On the other hand, inhibiting the mTOR pathway is mentioned, besides other importing effects, to slow down aging.
Does that mean that I, a very active person in his 60ties, might stay healthy for longer but age faster and will die prematurely?

Posted by: Stephan at April 20th, 2019 11:52 PM

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