Sarcopenia is a process of aging that means a decrease in muscle strength and function due to a decrease in skeletal muscle [1]. From a pathophysiologic perspective, sarcopenia can be considered an organ failure which can develop chronically or acutely [2]. Clinical studies indicate that sarcopenia is associated with a decreased walking ability, more frequent use of a cane, and difficulty in climbing, lifting, kneeling, or standing up from a chair [3-4]. Sarcopenia is a syndrome a risk of adverse outcomes such as physical disability, poor quality of life and death. In this research, we reviewed the literature to introduce the definitions and diagnostic criteria, pathophysiology and management of sarcopenia with clinical relevance for exercise physiologist. This study is designed to introduce the latest diagnostic methods of sarcopenia and is intended to help the elderly to organize exercise programs. The development of criteria for the diagnosis of sarcopenia is complex and must depend upon skeletal muscle mass and functional capacity in geriatric patients, this should draw health care provider. In addition, the effect of exercise being introduced as a preventive measure of sarcopenia is presented.

Sarcopenia was first coined by Irwin Rosenberg in 1989 is now widely accepted to describe the steady and involuntary loss of skeletal muscle mass during aging [8]. Although many challenges exist to make definition of sarcopenia, but until now, there is no consensus. Baumgartner et al. (1998) were the first define sarcopenia as the appendicular skeletal muscle/height² (ASM/h²) by measuring muscle mass as DXA (dual-energy X-ray absorptiometry) and set the case of less than two standard deviation of young healthy mean as the set-off point of sarcopenia [1]. Second definition of sarcopenia was developed by Janssen and colleagues. They measured SMI (%; total SMI [kg]/weight [kg]×100) using BIA (bio-electrical impedance analysis) [5]. Newman et al. (2003) indicated that the ASM/height² index primarily identified individuals with low BMI as sarcopenia [6]. Cruz-Jentoft et al. (2010) measured muscle mass as DXA and BIA, cut-off point was same as Baumgartner et al. (1998). Additionally, muscle strength and physical performance were evaluated as grip strength and gait speed or SPPB (short physical performance battery) [3]. Fielding et al. (2011) measured muscle mass using only DXA, and separated men (≤7.23kg/m²) and women’s standards (≤5.67kg/m²) with appendicular lean mass/height² (ALM/h²). It was defined as physical function was evaluated as gait speed but did not provide a standard for muscle strength [7].

In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) established sarcopenia definitions and diagnostic criteria [8]. EWGSOP defined sarcopenia as a gradual decrease in skeletal muscle mass and strength, and reduced muscle mass, strength and physical performance became diagnostic criteria [8]. The International Working Groups on Sarcopenia (IWGS) [7] and the EWGSOP [8] adopted the criterion based on DXA to define sarcopenia by Baumgartner et al (1998) [1].

In 2019, a revised EWSGOP2 has developed new consensus criteria [9]. In EWGSOP2, muscle mass is measured as BIA to calculate ASM/h² and body mass index and muscle strength is evaluated by hand grip strength. What makes EWGSOP2 different from EWGSOP is that it categorizes the severity of sarcopenia and sets new cut-off points [10].

Meanwhile, as Asia differs from Europe by ethnicities, cultural and lifestyles, diagnostic criteria of Asian Working Group for Sarcopenia (AWGS) different from EWGSOP are introduced [11]. In AWGS, muscle mass was measured as DXA and BIA and the result calculated as skeletal muscle mass/h² was used as an evaluation variable, and muscle strength was evaluated as hand grip strength in the same way as EWGSOP. The AWGS was also revised in 2019, and criteria for questionnaire and calf circumference were introduced to help people easily recognize the risk of sarcopenia, and in addition, diagnostic methods such as 6-minute walking, SPPB, and chair stand test were defined [12].

Numerous epidemiological studies using different methods of measurement and cut-off points have attempted to establish the prevalence of sarcopenia. In general, 5-13% of population aged 60-70 years and 11-50% of population in their 80s have been assumed to have sarcopenia. Thus, 3.6 million persons in the USA were estimated to be with sarcopenia [13-16].

Various methods were introduced to assess sarcopenia. Measuring skeletal muscle mass is a very direct and useful way to assess sarcopenia. BIA and anthropometry are also very useful method and popular one to assess sarcopenia, because of the noninvasiveness and absence of radiation hazard. These electrical equipment measures electrical resistance, skinfold thickness and circumferences. These factors make it possible to predict muscle mass. However, the limitation is its vulnerability for hydration and systemic error while collecting data.

Recently, DXA, magnetic resonance imaging (MRI), and computed tomography (CT) were suggested to assess whole body skeletal muscle. However, these contain limitation of radiation exposure and cost issue [16].

Baumgartner et al. (1998) developed the operational definition of sarcopenia first [1]. The approach was defined as ASM (sum of the masses of arm and leg lean soft tissue from DXA) divided by height squared (also referred to as stature, ASM/S²). They used statistics to get cutoff values. The two standard deviation below sex-specific mean of the distributions in a reference sample of young and middle-aged adults from the Rosetta Study was the criteria [14]. Other studies reported sarcopenia prevalence in different age, racial and gender characteristics, using various method [17-18]. For example, Melton et al. (2000) proposed different sarcopenia index defined as total lean body mass/stature² [18], Janssen et al. (2004) used BIA to calculate the index defining total skeletal muscle/stature² in US population [5].

In EWGSOP2, ASM/h² and body mass index (ASM/BMI) calculated as BIA, and cut-off was set to <7.0kg/m² for men and <5.5kg/m² for women. In addition, cut-off point was set to ASM/BMI ratio less than <0.789 for men and <0.512 for women. On the other hand, muscle strength was evaluated as grip strength, and cut-off point was set to <27kg for men and <16kg for women [11]. Gait speed is used to classify the severity of sarcopenia [10].

AWGS evaluates muscle mass as DXA and BIA. Cut-off point of DXA is set to less than <7.0kg/m² for men and <5.4kg/m² for women. BIA was calculated as skeletal muscle mass/h² and set to less than <7.0kg/m² for men and <5.7kg/m² for women. The cut-off point of grip strength is <26kg for men and <18kg for women [12]. The criteria for calf circumference were <34 cm for men and <33cm for women, and the score criteria for questionnaires were also presented (SARC-F ≥ 4 or SARC-CalF ≥ 11). Finally, the modified AWGS (2019) should not only diagnose sarcopenia, but also monitor its potential [12].

Over the years, no relevant consensus has been reached to find the definition and diagnostic criteria of sarcopenia until now. However, the fact that the best measures are based on muscle strength rather than muscle mass particularly in the context of cardiovascular disease has been confirmed [19].

Sarcopenia can cause various clinical problems, such as loss of strength, mobility disorders, disability, and poor quality of life [4, 10, 20-22]. Various factors including vitamin D deficiency, pro-inflammatory cytokines, decreasing growth hormones etc., can cause sarcopenia [7].

The role of apoptosis in post-mitotic tissues such as skeletal muscle is not clearly understood [23]. From the cellular level, studies proved that different conditions leading to muscle wasting involved different cell signaling pathways that might lead to programmed cell death (apoptosis), increased protein breakdown, or even decreased activation of the satellite cells responsible for muscle regeneration (Figure 1).

Mauro (1961) observed a group of mononucleated cells at the periphery of adult skeletal muscle myofibers by electron microscopy. These were named satellite cells due to their sublaminar location and intimate association with the plasma membrane of myofibers. The direct juxtaposition of satellite cells and myofibers immediately raised a hypothesis that these cells may be involved in skeletal muscle growth and regeneration [24]. Homeostatic and regenerative replacement of skeletal muscle fibers requires the activity of satellite cells. Satellite cell function is controlled by both intrinsic and extrinsic regulatory cues, and pathological deregulation of satellite cell function has been proposed to play an important role in age-dependent deterioration of muscle function and in muscle dystrophic disease. However, satellite cell transplantation to enhance muscle repair or restoration has little data in the literature.

It is very clear that sarcopenia is positively associated with various physical and physiological problem, but the problem is that it is very hard to know which one comes first. However, aging is the prime factor for this condition. Recent studies described the detailed mechanism of the sarcopenia in the elderly and found that one of the most prominent causes of sarcopenia is inactivity [25] (Figure 2). Exercise stimulates the release of muscle growth factors to activate satellite cells and protein synthesis. The regenerated muscle can delay the aging process. In other word, aging process accompanied by sarcopenia can be accelerated by immobilization. Sarcopenia can be aggravated by itself, because of the decreased physical function can also cause sarcopenia.

Sarcopenia is an emerging problem considering the rapid growth of the elderly population these days. To reduce the socioeconomic, it is critical to focus on sarcopenia, which is aging related condition resulting in skeletal muscle loss. Pathophysiology illustrates that sarcopenia is strongly associated with gerontology and its accompanying problems. A multidisciplinary approach including nutrition, exercise and medical management are essential to approach effectively treat this emerging condition. In addition, exercise intervention is an economical and cost-effective method of prevention, so exercise specialists need to understand the characteristics of sarcopenia and construct exercise programs. In a future study, it is necessary to find a more effective exercise program by applying various programs introduced as exercise intervention for the elderly and comparing them with the diagnostic criteria of sarcopenia.