Skeletal muscle memory: Recall for healthy aging

Learn about the critical role of skeletal muscle in overall health, and the importance of maintaining muscle mass as we age to support longevity and combat age-related conditions

Skeletal muscle tissue is critical for locomotion, breathing, and as a storage site for carbohydrates and fats. The largest deposits of amino acids in the body are stored in skeletal muscle, serving to mitigate disease risks and improve outcomes should an infection, hospitalization, or surgical procedure occur. ^(1-7) Retention of muscle size as we get older is essential for whole-body health and is one of the most important factors to living years spent in good health, known as ‘healthspan’. ⁽⁸⁾

An unavoidable outcome of aging is the natural loss of skeletal muscle size and inability to perform daily activities due to a process called sarcopenia – a term derived from the Greek language meaning ‘flesh’ (sarx) and ‘loss’ (penia). ⁽⁹⁾ In sedentary (inactive) individuals, the onset of sarcopenia can start before middle age and leads to performance and metabolic dysfunction. Maintenance of muscle health is closely linked to survival during the aging process and is therefore paramount to maintaining mobility and self-reliance with aging.

Accruing muscle mass – hypertrophy – has gained popularity with the rise of bodybuilding and ‘competitive fitness’ and is an increasingly desired outcome of gym patronage. Fortunately for those who choose to lift weights, muscular function is among the greatest predictors of healthspan and lifespan. ^(10,11) The health benefits of weightlifting that improve long-term quality of life include high muscular function, preserving the muscle-to-brain connection (i.e., innervation), and maintaining fast contracting and powerful muscle fibers. ⁽¹²⁾ Collectively, these benefits can serve to enable reactive movements such as quickly recovering balance to prevent a fall. Falls in older age are one of the leading causes of loss of mobility and mortality. ⁽¹³⁾ Falls result in a rapid healthspan decline and loss of independence due to further loss of muscle mass and function. These risks can be altogether mitigated through early adoption of a muscle-centric approach to fitness. A rebound in muscle health becomes harder to accomplish with age; however, increasing the size and performance of our muscles at any age may offer a type of ‘memory’ for our muscle cells to recall when we inevitably experience injury, illness/disease, or a shift in life priorities.

Skeletal muscle has a ‘memory’ to recall prior exercise adaptations

The internal environment of skeletal muscle is influenced by volume and the type of external stimulation. In fact, all living organisms are governed by the SAID principle (Specific Adaptations of Imposed Demands). The SAID principle gives rise to the varied adaptations associated with different modes of exercise (i.e., resistance, endurance, concurrent). Resistance training (e.g. barbells, dumbbells, cable assisted machines, etc.) uses progressively heavier weights and/or increasing volume to increase muscle size and function, while endurance training (e.g. running, cycling, swimming, etc.) uses long duration low-resistance repeated movements to drive metabolic changes in muscle that increase energy production capacity via the addition of mitochondria (the powerhouse of the cell). Concurrent exercise is the combination of both resistance and endurance training that benefits muscle growth and energy production.

Regardless of training type, exercise alters the cellular and molecular characteristics of skeletal muscle. Changes to these characteristics after exercise training serve as a biological ‘save point’ for skeletal muscle health. In short, some changes to the skeletal muscle environment after exercise training are ‘stored’ within specialized cellular (i.e., muscle fiber nuclei, or myonuclei) and molecular (i.e., epigenetic) components. The imprint exercise training leaves on these components in muscle serves as a blueprint for future skeletal muscle adaptation. The current evidence for this ‘muscle memory’ is most compelling for resistance training. ^(14-16) It is currently unclear how long ‘muscle memory’ might last; however, it may serve to kickstart the biological machinery for improved muscle health upon resuming exercise training. In other words, past exercise training rewires the cellular and molecular components of muscle to create a tissue that is more adaptive to future training after periods of inactivity (i.e., injury, illness, hospitalization, etc.)

Exercise demands specific changes that become imprinted in our cells as an efficient progress-saving feature

If we consider our DNA as the overall blueprint for all things created in the body, the blueprint then guides the instruction manual for each specific job at each stage of the building process. To drive efficient work patterns, the blueprint can be highlighted, bolded, and otherwise bookmarked for easier navigation. Each time we exercise, we signal for very specific instructions to be called upon to build healthier muscle tissue. To make the process more efficient, our DNA is chemically tagged through a process called ‘methylation’. DNA methylation serves to signal an exercise-related gene to turn on or off with training. Recent evidence from our lab and others suggests that two to three months of disuse does not erase DNA methylation changes in muscle caused by previous exercise training prior to disuse. ^(14,17,18) If epigenetic ‘muscle memory’ lasts longer than a few months, it could have important implications for muscle adaptive potential in old age, when muscle becomes harder to build and maintain.

Concluding remarks

Aging is an inevitable lifelong process, but we can improve our healthspan by limiting the loss of bodily function through consistent exercise. Perfect consistency is not realistic, and as such, we should rest assured that our efforts are not lost during these brief lapses that happen to us all. Thankfully, it seems muscles have a built-in ‘auto- save’ feature for these setbacks that can reduce negative consequences and help return to a healthier state more efficiently. Starting the building process earlier allows more time and capitalizes on younger muscle’s high level of plasticity (i.e., muscle’s ability to respond and adapt to stimuli). Even when adopting an active lifestyle later in life, there is still sufficient muscle plasticity to limit setbacks and promote muscle health. Still, an active lifestyle that incorporates resistance training is one of the best ways to take advantage of ‘muscle memory’ and may promote youthful characteristics even in old age.

Authors: Toby L. Chambers*, Nathan Serrano*, and Kevin A. Murach†

*Co-authors contributed equally

†Corresponding author

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