Muscle degeneration: a consequence of the aging process that impacts the quality of life

 Highlights:

• Sarcopenia is a progressive decline in skeletal muscle mass, function, and strength, leading to an increased risk of fall, injury, and mortality
• Sarcopenia can be classified into primary (age-related) and secondary (other conditions)
• Age-related muscle decline can be attributed to genetic, environmental, and lifestyle factors, which lead to a reduction in muscle fibers, motor function, and molecular repair pathways
• Age-related muscle degeneration contributes to conditions that influence longevity, like cardiovascular diseases and type 2 diabetes
• Nutrition, physical activity, and nutritional supplementation might slow down the muscle degeneration process

Introduction

The aging process carries several extensive changes to the human body. One such change is the progressive loss of skeletal muscle mass, function, and strength over the years (sarcopenia). Maximum muscle mass is attained in the second decade of life, after which a gradual decline takes place. Research suggests that from the third decade up till the sixth, the muscle mass decreases by a rate of 3–8% per year. This rate of decline is even higher for those over 60 years of age. The reduction of muscle mass is accompanied by a decrease in muscle function and strength.

Causes of sarcopenia

There are many elements that contribute to sarcopenia, like genetic, environmental, and lifestyle factors(1). In addition, many pathways play a role in and contribute to sarcopenia, such as insulin signaling, inflammatory processes, and disruption of proteostasis (2). Research suggests that changes in metabolic functionality are a significant contributor to sarcopenia. This is likely because the skeletal muscle constitutes up to 50% of mammalian tissue, making it an important site that plays a role in carbohydrate, protein, and fat metabolism (3). For example, literature shows that alterations in the muscle protein-synthesis capacity are one of the metabolic contributors responsible for sarcopenia (4).

In addition to the previous, research has highlighted that the decrease in lean muscle mass (the primary source of body proteins) is driven by a decline in the numbers of type II muscle fibers (fast-twitching fibers, which are larger, possess greater contractility and supports power activities compared to type I, but quicker to be fatigued) (5). These fibers have a lower density of mitochondria, myoglobin (oxygen carrier in muscle), capillaries, and oxidative capacity (2, 5). In addition, the expression of the contractile protein myosin heavy chain (actin-based proteins that convert chemical energy into mechanical force) in type II fibers has been found to decrease with age, producing the said effect.

Research has also implicated the decline in neuron motor cells function and number as a contributor to the age-associated reduction in muscle mass (5). In this context, the literature has highlighted that aging brings about a decline in axonal cell body size and neuromuscular junction instability, promoting dystrophy (2). All these effects are aggravated by a decline in mobility associated with aging.

On a molecular level, there is an imbalance in the activity of Notch (regulator of muscle formation) and Wnt (signaling molecule involved in muscle cell differentiation) signaling pathways (2, 6). Under normal circumstances, the Notch pathway is activated upon muscle injury to recruit cells that help regenerate the muscle, after which Wnt activates to help cells differentiate. With aging, the balance of the process is disturbed, leading to impaired differentiation (6). Further research revealed that there is an increased rate of telomere shortening in the recruited cells in addition to DNA damage.

Depending on the causative factor, sarcopenia can be divided into primary and secondary sarcopenias (2, 7). Primary sarcopenia, or age-related sarcopenia, is attributed to the aging process. Secondary sarcopenia results from one or more factors like the lack of physical activity (limited mobility or bed rest), malnutrition and inadequate intake of proteins (undernutrition, overnutrition, obesity, or malabsorption), and disease conditions (neurological disorders, inflammatory conditions, and malignancy) (7).

Consequences of sarcopenia on aged individuals

The involuntary loss in muscle mass and functions accompanying the aging process brings about a change in body composition. This change is manifested by a progressive increase in body fat composition, which increases the risk of developing age-related diseases like type 2 diabetes and cardiovascular disorders (8). Other reasons that contribute to the development of the said diseases arise from the decrease in physical activity, nutritional deficiencies, and inflammation associated with the aging process (4).

In addition to the previous, there is a decrease in bone density and increased joint stiffness, leading to conditions such as osteoporosis (2, 8). This leads to an increased risk of fall, bone fracture, and disability, making sarcopenia a significant contributor to frailty, morbidity, and mortality.

Another consequence associated with sarcopenia and aging is the disturbance of the thermoregulatory processes of the body. Evidence from the literature highlights that the lost muscle mass affects the body both in cold and warm environments (9). For example, lower muscle mass has been found to impair peripheral insulation in a cold environment and decrease thermoregulation capacity. Also, the reduction in muscle mass due to the aging process has been linked to a decrease in blood volume, impacting exercise capacity and heat stress. 

Assessing age-related muscle degeneration and exploring techniques to slow it down

Age-related muscle degeneration has recently received formal recognition as a disease. Several approaches have been suggested to diagnose it, one of which is the FACS algorithm (2). FACS is explained as follows: 

• The "F" pertains to "finding" the case, 
• The "A" denotes "assessing" the condition via grip strength, 
• The "C" refers to "confirming" in terms of muscle quantity of strength, 
• The “S” indicates “severity” checked using muscle performance. 

This means that regular monitoring and assessing of individuals could help slow down the effect of the condition (2, 7).

Interventions like physical exercise and nutrition have been explored as means to slow down the effect of age-related muscle degeneration. For example, exercise has been found to improve muscle mass and function (10, 11). Literature has highlighted that older adults performing aerobic physical activities have been found to possess higher quadriceps muscle volume and increased muscular fiber. In the same context, research revealed that resistance training is more beneficial in increasing muscle mass and strength. In contrast, endurance training shows better results in terms of improved muscle performance and prevention of future disability (12). The improvement in muscle capacity is attributed to exercise-driven muscle growth through muscle tissue buildup. In addition to improved muscle strength and capacity, the literature has highlighted that exercise plays a role in counteracting some of the mechanisms contributing to muscular atrophy (2, 13). For example, exercise has been shown to decrease inflammation, increase the recruitment of cells involved in muscle buildup, and reduce fat infiltration. Structural improvement has also been suggested among the beneficial effects of exercise (2, 14).

Nutritional interventions usually focus on the protein portion of the diet to compensate for muscle loss. Studies have highlighted the benefits of supplementing essential amino acids (these are amino acids that cannot be produced by the body and are derived from sources like eggs, beef, dairy, soy, and wheat)(6). When the latter was combined with resistance training, significant results were achieved in terms of attenuating age-related muscular degeneration (15). In the same context, protein consumption within 60 minutes of exercise was found to produce the best results in terms of effects on muscle building and maintenance (12). The literature also highlighted that vitamin D supplementation and polyphenols (contained in berries, nuts, apples, beans, and others) were found to reduce inflammation and improve metabolic parameters, promoting muscle function (6). In addition to the previous, caloric restriction has also been shown to benefit skeletal muscles by reducing autophagy (16). Considering the benefits of using amino acids, the caloric restriction approach should be used while maintaining a sufficient protein supply. This is because excessive caloric restriction in the elderly can have the opposite effect and contribute to muscle loss, decreased body mass index, and increased risk of disability and mortality (17).  It is important to note that the impact of nutrition is still in the investigational stage, and further research is needed to understand this role fully.

In addition to the previous, nutritional supplementation with compounds like Urolithin A (UA) has also demonstrated promising results. Studies on mice models show that supplementation with UA increased muscular activity and performance (18). In the same context, studies performed on human subjects showed promising results in terms of improved physical functioning manifested in reduced muscle decline (19). Further research is needed to validate these results.

Tips

You can suggest several tips to help your clients reduce the impact of sarcopenia on their muscle mass and function. The following is a non-exhaustive list of suggested tips.

• Explain to your clients that sarcopenia is a natural part of the aging process that can be slowed down.
• Advise your client to maintain physical activity (combine resistance training with nutrition for the best outcome) to reduce the impact of age-related muscle degeneration.
• Recommend your clients to take proteins (in diet or as supplements) within 60 minutes of exercise.
• Highlight the importance of consuming fruits and vegetables, as they reduce the impact of aging on the muscles.
• Explain to your clients the possible benefits of using supplements that support the muscles, such as those containing UA. However, be sure to explain that most of the results about their impact are still experimental.

Conclusions

Primary sarcopenia is characterized by a decline in muscle mass and strength, among others. It usually arises from an increase in muscle turnover and a decrease in repair capacity attributed to the aging process. There are many contributors to the condition, like genetic, environmental, and lifestyle factors. The decline in muscle mass increases body-fat composition, which, when coupled with other factors like reduced physical activity, leads to an increase in the risk of age-related disorders such as cardiovascular conditions. Many factors can be implemented to slow down the impact of aging on muscles, like physical activity, nutrition, and supplementation.

References

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2.            Wiedmer P, Jung T, Castro JP, Pomatto LCD, Sun PY, Davies KJA, et al. Sarcopenia – Molecular mechanisms and open questions. Ageing Research Reviews. 2021;65:101200.

3.            Sandri M. Autophagy in skeletal muscle. FEBS Letters. 2010;584(7):1411-6.

4.            Siparsky PN, Kirkendall DT, Garrett WE. Muscle Changes in Aging: Understanding Sarcopenia. Sports Health. 2013;6(1):36-40.

5.            Cade WT, Yarasheski KE. Metabolic and molecular aspects of sarcopenia.  Principles of Molecular Medicine: Springer; 2006. p. 529-34.

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10.          Harber MP, Konopka AR, Undem MK, Hinkley JM, Minchev K, Kaminsky LA, et al. Aerobic exercise training induces skeletal muscle hypertrophy and age-dependent adaptations in myofiber function in young and older men. Journal of applied physiology. 2012;113(9):1495-504.

11.          Bowen TS, Schuler G, Adams V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. Journal of Cachexia, Sarcopenia and Muscle. 2015;6(3):197-207.

12.          Phu S, Boersma D, Duque G. Exercise and Sarcopenia. Journal of Clinical Densitometry. 2015;18(4):488-92.

13.          Verdijk LB, Snijders T, Drost M, Delhaas T, Kadi F, Van Loon LJC. Satellite cells in human skeletal muscle; from birth to old age. Age. 2014;36(2):545-57.

14.          Narici M, Franchi M, Maganaris C. Muscle structural assembly and functional consequences. Journal of Experimental Biology. 2016;219(2):276-84.

15.          Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cachexia and sarcopenia: mechanisms and potential targets for intervention. Current opinion in pharmacology. 2015;22:100-6.

16.          Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Experimental gerontology. 2010;45(2):138-48.

17.          Xie W-Q, Xiao W-F, Tang K, Wu Y-X, Hu P-W, Li Y-S, et al. Caloric restriction: implications for sarcopenia and potential mechanisms. Aging. 2020;12(23):24441-52.

18.          Ghosh N, Das A, Biswas N, Gnyawali S, Singh K, Gorain M, et al. Urolithin A augments angiogenic pathways in skeletal muscle by bolstering NAD+ and SIRT1. Scientific Reports. 2020;10(1):20184.

19.          Liu S, D’Amico D, Shankland E, Bhayana S, Garcia JM, Aebischer P, et al. Effect of Urolithin A Supplementation on Muscle Endurance and Mitochondrial Health in Older Adults: A Randomized Clinical Trial. JAMA Network Open. 2022;5(1):e2144279-e.

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