|Year : 2020 | Volume
| Issue : 2 | Page : 62-65
Sarcopenia: A review
Sr Consultant and Emeritus Professor of Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India
|Date of Submission||25-Jun-2020|
|Date of Acceptance||03-Nov-2020|
|Date of Web Publication||15-Dec-2020|
Dr. O P Gupta
Sr Consultant and Emeritus Professor of Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, (Wardha), Maharashtra - 442 102
Source of Support: None, Conflict of Interest: None
Sarcopenia is the process of loss of skeletal muscle mass. It has recently been recognized as a separate entity, and there is very little awareness about it among health professionals. Sarcopenia is a geriatric condition where there is an age-related primary loss of muscle mass, although it has now been recognized to begin early in life. In general, loss of muscle mass occurs secondary to chronic illness, malignancy, or drugs, particularly long-term steroid therapy and cytotoxic drugs. Aging itself may cause sarcopenia, especially in inactive individuals who have a sedentary lifestyle. There is a decrease in muscle mass with increase in intra- and intermuscular adipose tissue. Besides epigenetic factors, malnutrition, chronic inflammation (raised cytokine levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha), and changes at hormonal and mitochondrial level are responsible for the poor muscle growth and loss of muscle mass and strength and thereby affect the performance of activities of daily living. Diagnosis of sarcopenia can be made by simple clinical tests which detect loss of muscle mass and strength. Loss of muscle mass can be confirmed with the help of computed tomography, magnetic resonance imaging, and ultrasonography. Exercise and improvement of nutrition are the mainstays of treatment. So far, no specific drug is available for the treatment of sarcopenia, though some age-old drugs such as metformin and anabolic steroids have been tried with variable results. Some new molecules have shown positive results in experimental animals and are in various phases of clinical trials.
Keywords: Elderly, geriatrics, muscle mass, sarcopenia
|How to cite this article:|
Gupta O P. Sarcopenia: A review. J Mahatma Gandhi Inst Med Sci 2020;25:62-5
| Introduction|| |
Sarcopenia is a geriatric syndrome characterized by decrease in muscle mass and muscle strength, affecting physical performance and quality of life. Sarcopenia is a Greek word (sarx = flesh and penia = loss) which means “loss of muscle mass.” It was coined by Rosenberg in 1989. Sarcopenia has been defined as a progressive and generalized skeletal muscle disorder associated with accelerated loss of muscle mass and function. This consequentially leads to increased adverse outcomes such as falls and fractures, frailty, functional decline, loss of independence, lower quality of life, increasing risk of hospitalization, and mortality. The Asian Working Group for Sarcopenia by consensus defined sarcopenia as a low muscle mass plus low muscle strength and/or low physical performance. In 2017, sarcopenia has been assigned an ICD-10-CM Code of M62.84.
| Pathophysiology|| |
The muscle tissue is not static. It exhibits a continuous process of atrophy and hypertrophy. It undergoes a cyclical process of death and rejuvenation. The proteins degrade, and the muscle cells undergo apoptosis. The incorporation of amino acids, synthesis of protein, and the stimulated stem cells which produce satellite cells are capable of repairing the damaged muscle and subsequently causing the growth of the muscle.,
The mass and the strength of muscles grow from birth up to the third decade. After the third decade, decline in muscle mass starts, and this subsequently leads to age-related sarcopenia. Even physically active persons have been found to have around 3%–5% loss of muscle mass per decade. Loss of muscle mass is more in physically inactive persons. The loss of muscle mass has been found to be more rapid after the seventh decade. The prevalence of sarcopenia in the US and Europe rises from 5% to 13% in patients of 60–70 years to 11%–50% in those over 80 years. In an Indian study, the prevalence of sarcopenia among individuals was found to be 14.2% in elderly population above the age of 60 years and higher in females.
Several factors have been implicated in the development of sarcopenia [Figure 1]. These include age-related loss of muscle mass, malnutrition, sedentary lifestyle, Vitamin D deficiency, hormonal changes (testosterone, insulin-like growth factor [IGF-1]), increased cytokines (inflammation), decreased motor unit activity, overexpression of myostatin, atherosclerosis, and obesity.
|Figure 1: Factors affecting skeletal muscles and leading to development of sarcopenia|
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In elderly people, age-induced anorexia, feeding difficulties due to oral problems, or loss of taste are associated with malnutrition. Further, immobility or sedentary habits lead to decreased protein synthesis and motor unit remodeling. While atherosclerosis results in relative reduction in blood supply, the presence of inflammatory cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha), results in decrease in muscle strength. Fat accumulation in muscles or myosteatosis is responsible for decline in muscle strength as well as its functions. The epigenetic alterations and mitochondrial dysfunction also lead to reduced muscle mass and strength. Alterations in hormonal levels (low testosterone, insulin growth factor-1 [IGF-1], and growth hormone) in advancing age are related to sarcopenia. Muscle strength also declines due to reduced production of apelin, an endogenous peptide induced by muscle contractions. Agrin, which mediates acetylcholine receptor clustering required for function of neuromuscular junction, gets proteolyzed to C-terminal agrin fragments, and its level is elevated in sarcopenia. Angiotensin II causing endothelial dysfunction, ischemia, inflammation, and mitochondrial dysfunction affects skeletal muscles adversely. Trials with angiotensin-converting enzyme-1 (ACE-1) have shown functional improvement.
| Clinical Features|| |
Sarcopenia can be acute (lasting for <6 months) or chronic (lasting for >6 months) depending on the causes. However, aging-associated sarcopenia is chronic. Based on clinical manifestations, sarcopenia is further classified into:
- Presarcopenia: Low muscle mass without impact on muscle strength or physical performance
- Sarcopenia: Loss of muscle mass and muscle strength
- Severe sarcopenia: Loss of all the three, i.e., muscle mass, muscle strength, and physical performance. In some cases, when the muscle strength is low, the case is labeled as probable sarcopenia
- Sarcopenic obesity – in obesity, there is an increase of fat infiltration in the muscles, thereby decreasing the functions of the muscle.
| Diagnostic Methods|| |
Various tests have been developed for the screening of the elderly. A questionnaire which has been developed for assessing the quality of life in sarcopenia can be used for initial screening. The questionnaire has been translated into different languages of the world, including Hindi and Marathi. It has 22 simple questions which can be answered in 10–15 min. Ishii et al. developed a model to estimate the probability of sarcopenia which included three variables: age, grip strength, and calf circumference. The authors created a score chart for each gender based on the final model. When the sum of sensitivity and specificity was maximized, the sensitivity, specificity, and positive and negative predictive values for sarcopenia were 84.9%, 88.2%, 54.4%, and 97.2% for men and 75.5%, 92.0%, 72.8%, and 93.0% for women, respectively.
To further assess the individual after screening, anthropometric measurements such as body mass index (BMI), mid-arm circumference, and skin-fold thickness should be recorded. Some studies have included the calf circumference since it also correlates well with the nutritional status, like the mid-arm circumference. To assess the integrity of the musculoskeletal system, certain objective tests are carried out to assess mobility, strength, and balance, such as anthropometric measurements, gait speed, handgrip, and ability to rise from a chair. Some other tests are as follows:
- Height and weight of the person to calculate the BMI
- For skeletal muscle mass, usually dual-energy X-ray absorptiometry (DEXA) is used. However, DEXA may not be available everywhere, and the mid-arm circumference and calf circumference correlate very well to the skeletal muscle mass.
- Mid-arm circumference: The subject raises the arm at shoulder level with the elbow bent at 90° angle. The subject flexes the biceps, and measurement is taken at its greatest girth
- Calf circumference: The subject stands with feet apart (at shoulder width). Calf circumference is measured at its greatest girth.
Recently, computed tomography (CT) and magnetic resonance imaging (MRI) have been used to assess the skeletal muscle mass. CT and MRI are gold standards for the muscle mass measurements but used sparingly. The muscle mass so measured is divided by weight square and presented as kg/m2. In the European population, this is reported to be <7 kg/m2 in males and <15 kg/m2. It is always better to measure muscle mass in the normal population of each region. The average maximum and minimum derived from these populations will be more accurate. Similar steps should be taken for all other measurements.
Other methods to assess muscle mass such as bioelectrical impedance analysis, mid-thigh imaging, third lumbar vertebral imaging, and psoas muscle measurement have also been used in other studies. More recently, ultrasound assessment has been considered to be more reliable. In a pinnate muscle (quadriceps), it can measure thickness and cross-sectional area and fascicle length. The echogenicity reflects the noncontractile tissue and myosteatosis.
- Grip strength: A dynamometer is usually used to measure handgrip strength. Grip strength is measured from each hand. A minimum of three readings are taken with some resting interval and the highest reading is recorded. The cutoff for handgrip is reported to be <26 kg (26–30 kg) in males and <16 kg (16–20 kg) in females.
In case a dynamometer is not available, a relatively simple method has been used. The subject is asked to lift 1 kg weight with the arm lifted above the shoulder, with the elbow being fully extended for a period of 30 seconds. This is a well-validated method to assess the proximal muscles of the upper extremity. If the subject is able to maintain a weight of 1 kg for 30 s or more, grip strength is considered normal.
For the proximal muscles of the lower limb, another test is used. This involves rising to a standing position from a standard chair without arm support within 30 s. One internally rotates the arm and flexes elbows in front of the chest and attempts to rise as many times as one can in 30 s. Normally, one should be able to rise from a chair five times in 30 s.
- Speed and balance test: A 4-m gait speed test is utilized for this purpose. The subject is asked to walk on a flat surface for a distance of 4 m, and the time is noted. In general, a normal person should be able to cover this distance in <5 s, i.e., <0.8 m/s. If a person takes longer than this, then the performance is considered subnormal. This also tests the balance.
Other tests to evaluate the performance, balance, and endurance are also used. In timed up and go test, an individual gets up from chair, walks for 3 m, turns back, walks again, and sits down. Other tests are a walk of 6 min, or a 400-m walk time, climbing up the stairs, etc., and shown to be well correlated to physical performance [Figure 2].
| Management|| |
The musculoskeletal system and physical capabilities decline with age. Our strategies for management should be to enable the individual to participate in activities of daily living (ADL) and instrumental activities of daily living (IADL). Nonpharmacological treatment is always preferable since the patient might already be on multiple drugs for his other ailments. Further, there is no specific drug effective in overall improvement in sarcopenia per se. Moreover, a number of studies have shown good results with exercise and supplementary nutrition. Of course, the treatment of comorbid conditions, namely diabetes, hypertension, ischemic heart disease, tuberculosis, rheumatoid arthritis, or any malignancy, is essential. Some of these conditions also cause severe muscle wasting with or without loss of fat and lead to cachexia. Cachexia needs to be differentiated from sarcopenia. All cachexic patients are sarcopenic, but all sarcopenic patients are not cachexic.
Sarcopenic patients may have protein, calorie, mineral, or micronutrient deficiency resulting in a loss of muscle mass. Muscle tissue requires protein for its growth and strength. Good quality of protein is required for growth and maintenance in all age groups. Protein needs to be supplemented in the elderly if there is a definite history of unbalanced diet. There are several studies showing a positive outcome of supplementation of protein and muscle growth. Protein in the form of dairy products (especially whey protein), pulses, legumes, soya, egg and meat are good, as they contain essential amino acids. 1 g/kg body weight of protein per day is sufficient. However, those who have severe deficit may have 1.2–1.5 g/kg body weight if kidney functions are normal. Vitamin D supplements may increase the muscle strength. However, there are no consistent results among various studies. Omega-3 fatty acids supplemented through seafood or fish oil consumption may directly signal muscle growth and may prevent muscle mass losses through anti-inflammatory action. Recently, creatine added in diet and exercise resulted in muscle growth.
Exercise is the mainstay in the management of sarcopenia. Depending on the capability of the individual, a beginning can be made from whatever level he or she can perform. In fact, all types of exercise should be done, starting slowly with low-intensity training and gradually increasing as per tolerability. Resistance exercises such as weight lifting, pulling against resistant band, or moving body parts against gravity can be used. Resistance exercises are useful as the tension on muscle fibers results in growth signals that cause the muscle cells to grow and repair themselves. The stem cells or the so-called “satellite cells” get activated and reinforce the muscle and increase the muscle strength and mass. Similarly, aerobic and endurance exercises such as jogging, cycling, and treadmill are equally beneficial. Walking can also prevent or reverse sarcopenia.
As far as pharmacological treatment is concerned, there is no specific drug available for sarcopenia so far. Hormonal deficit has been known to be responsible for loss of muscle mass. Replacement of hormones has been attempted, though no uniform beneficial results have been reported. Dehydroepiandrosterone and human growth hormone have little effect. Growth hormone is reported to increase muscle mass but without improving strength and function. IGF-1 also shows physiological results similar to growth hormone. Anabolic steroids and testosterone have shown some positive effects. They increase muscle mass as well as strength, but the adverse effects overweigh the beneficial effects. Recently, a clinical trial of selective androgen receptor modulator showed an increase in total lean body mass with improvement in physical functions.
Recently, certain exercise mimetics, which produce effects of exercise without actual exercise, like peroxisome proliferator-activated receptor agonists such as pioglitazone or similar drugs, and AMP-activated protein kinase agonists, enhanced running endurance in mice. Metformin has been studied as a potential pharmacological intervention to delay aging and the incidence of age-related sarcopenia. Phase II trials of myostatin antibodies are reported to increase muscle mass and some physical performance in older patients. Similar results were obtained with bimagrumab in a Phase II trial. Supplementation of creatine in diet is also associated with increases in lean tissue mass and muscle strength., Other compounds such as ACE inhibitors, thalidomide, and ghrelin analogs are also undergoing trials.
Some herbal products have also been reported to have beneficial effects on skeletal muscles. These are curcumin (derived from the common spice Curcuma longa), extracts from Withania somnifera, catechins, proanthocyanidins from grape seeds, ginger (Zingiber officinale), etc., Recently, ursolic acid from apple peels and tomatidine from green tomatoes have been reported to reduce muscle atrophy and increase muscle mass.
| Conclusion|| |
Sarcopenia, an age-related disease associated with decreased muscle mass, muscle strength, and physical performance, may lead to decreased ADL, IADL, recurrent falls, and frailty. These patients may require hospitalization. This condition needs to be recognized and investigated. Although there is no specific drug available for its treatment, motivation, nutrition, resistance, and aerobic exercise may help one to prevent, delay, or improve the physical performance.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]