Understanding sarcopenia: Pathophysiology, prevalence, and implications for clinical practice and public health

INTRODUCTION

As people live longer, they experience numerous physical changes. Among the most notable is the body’s reduced capacity to maintain balance, known as homeostenosis.^[1] This process involves the progressive degradation of muscle, bone, and fat tissues and is considered a hallmark of sarcopenia.^[2] Sarcopenia is now recognized as a progressive and generalized skeletal muscle disorder characterized by accelerated loss of muscle mass and function, which is linked to increased risks of falls, functional decline, frailty, and mortality.^[3]

Initially, the term sarcopenia was used to describe the age-related decline in muscle mass and function.^[4] For many years, however, it referred primarily to low muscle mass, often without taking functional impairment into account. This limited definition is still seen in some research areas, especially in studies focused on cancer or disease-related sarcopenia. Nonetheless, efforts to standardize the definition have led to significant progress. Several expert groups now emphasize the importance of muscle function in diagnosing sarcopenia. The most widely accepted criteria are those proposed by the European Working Group on Sarcopenia in Older People (EWGSOP), supported by the Asian Working Group on Sarcopenia (AWGS), and updated in EWGSOP2.^[3]

According to EWGSOP2, sarcopenia is diagnosed when low muscle strength is accompanied by low muscle mass or quality. It can be considered a form of skeletal muscle insufficiency or organ failure,^[1] which may present acutely, typically due to illness or immobility during hospitalization or develop gradually. Muscle mass and strength usually peak in young adulthood, followed by a plateau and then decline, with strength diminishing more rapidly than mass.^[4]

The World Health Organization (WHO) has recently adopted a function-oriented approach to aging, moving away from a disease-based model. This perspective emphasizes intrinsic capacity, referring to the combined physical and mental abilities of a person, and how these interact with the environment to determine overall function. Muscle strength is crucial to achieving and maintaining this capacity and should be monitored throughout life.^[5]

In practice, sarcopenia is often thought to affect only those with low body weight. However, it can also co-occur with obesity, a condition known as sarcopenic obesity, which significantly contributes to disability and mortality.^[6] Sarcopenic obesity involves both reduced muscle mass and increased fat mass and can go undetected when clinicians focus only on obesity. This complicates management and worsens outcomes.^[7] The development of both sarcopenia and obesity shares common pathogenic pathways. In sarcopenic obesity, muscle loss may heighten the risk of death and functional decline, particularly during weight loss efforts.^[7]

Sarcopenia is thus defined as a geriatric syndrome, a prevalent, complex, and costly health concern. It leads to higher morbidity and mortality rates, mobility limitations, increased fall and fracture risks, and decreased capacity for daily activities, ultimately causing functional disabilities and loss of independence.^[1]

This review aims to consolidate recent insights into sarcopenia, including its pathophysiology, diagnostic criteria, prevalence, and implications for clinical practice and healthcare systems.

EPIDEMIOLOGY

Sarcopenia, officially classified as a separate illness by the WHO in 2016 under the International Classification of Diseases, Tenth Revision, Clinical Modification code M62.84,^[8] remains a significant public health concern due to the difficulty in accurately estimating its prevalence. This challenge arises from varying diagnostic criteria and differences in sample characteristics across populations. Reported prevalence rates range widely, from 0.1% to 85.4% in adult populations.^[9]

Epidemiological data indicate that sarcopenia is more common in men, older adults, nursing home residents, individuals with low body mass index (BMI), and those with lower educational levels. In addition, U.S. ethnic minorities show higher rates, while individuals with darker skin than Caucasians exhibit lower rates.^[10] Cruz-Jentoft et al.^[1] reported sarcopenia prevalence in community-dwelling elderly ranging from 1% to 29%, influenced by age, diagnostic methods, and cut-off values. The EWGSOP, the Foundation for the National Institutes of Health, and the International Working Group on Sarcopenia have all reported varying prevalence based on differing definitions.^[11]

Batsis and Villareal^[7] found sarcopenia prevalence ranging from 4.4% to 94% using eight diagnostic methods. Bijlsma et al.^[12] identified rates from 0% in younger populations to 45.2% in those over 70. Studies reveal that using only muscle mass as a criterion typically yields higher prevalence than definitions incorporating strength and physical performance, as recommended by EWGSOP.

Further disparities stem from the diagnostic tools and cutoff values used. Beaudart et al.^[10] reported a prevalence range of 8.4–27.6% depending on measurement tools. In addition, sarcopenia often coexists with obesity, diabetes, osteoporosis, and osteopenia and may even precede these conditions.

In resource-limited settings such as Nigeria and other African countries, low awareness among healthcare providers contributes to underdiagnosis. Despite its impact, sarcopenia often remains unrecognized, with estimates reaching 15% in those over 65% and 50% in individuals over 80.^[13]

ETIOLOGY AND PATHOGENESIS OF SARCOPENIA

Sarcopenia is the result of a wide range of risk factors and mechanisms that are brought on by the person’s overall health and the environment.^[11] Among the most significant are lifestyle behaviors, including physical inactivity, smoking, and unhealthy eating habits, as well as age-related hormonal and cytokine changes. Other than these, the medications one takes, if any, may be the other cause of sarcopenia.^[11] The mechanisms that are thought to be the underlying cause of sarcopenia include changes in the muscle protein turnover that leads to muscle remodeling and also the loss of alpha motor neurons, the new cell recruitment by muscle, and the increased number of apoptotic cells.^[11] The hereditary factor is irrefutably known as an influencing element on the treadmill of muscle flammability and is to be regarded as the main source of both individual and population-related variations. However, the exact weight of each factor remains unclear.^[11]

CLASSIFICATION OF SARCOPENIA

Sarcopenia is classified into two which are primary or secondary. Primary sarcopenia is also known as age-related sarcopenia occurs when no particular reason is identified apart from the aging process. On the other hand, secondary sarcopenia is due to one or more identifiable reasons other than the aging process. Subcategories of secondary sarcopenia include disuse sarcopenia, disease sarcopenia, and nutrition/starvation-related sarcopenia. It arises due to suboptimal development during early life, poor diet, advanced bed rest, sedentary lifestyle, chronic illnesses, and certain medications.^[19]

CAUSES OF SARCOPENIA

Sarcopenia is a multifactorial condition arising from a complex interplay of nutritional deficiencies, physical inactivity, underlying diseases, and iatrogenic factors.^[19]

Nutritional deficiencies primarily lead to the development of sarcopenia. Regular protein or energy intake, together with specific nutrient insufficiencies, can ruin the muscle cells or stop the restoration of the cells from being effective. Besides, factors such as malabsorption of nutrients due to gastrointestinal problems, and age-related anorexia, which is often coupled with oral or dental issues, cause the appearance of muscle wasting as well.^[19]

Disease-related causes encompass a wide range of chronic health conditions. Musculoskeletal disorders, including bone and joint diseases, compromise mobility and physical function. Cardiorespiratory conditions, such as chronic heart failure and COPD, are associated with reduced physical capacity and systemic inflammation. Metabolic disorders like diabetes, endocrine imbalances, particularly those involving androgen deficiency; neurological conditions, cancer, and liver or kidney dysfunction all negatively impact muscle health through various mechanisms, including inflammation, hormonal disruption, and decreased activity levels.^[19]

Moreover, the contributions from medical sources of sarcopenia are numerous despite being able to be easily avoided. They include both hospital stay and the irreversible effects of a number of drugs. The patient’s hospitalization may be a forced one, usually leading to very little or no body movement, while the drug may hinder muscle metabolism directly or indirectly.^[19]

Collectively, these factors interact to accelerate muscle loss, emphasizing the need for a comprehensive approach to prevention and management.^[19]

STAGES OF SARCOPENIA

Sarcopenia can be staged to reflect its severity, which assists in guiding clinical management. The EWGSOP proposes three stages: presarcopenia, sarcopenia, and severe sarcopenia.^[1]

1. Presarcopenia is characterized by reduced muscle mass without an associated decline in muscle strength or physical performance. This stage is typically identified through precise muscle mass measurements compared to standard reference populations.

2. Sarcopenia is diagnosed when there is low muscle mass along with either reduced muscle strength or poor physical performance.

3. Severe sarcopenia is present when all three criteria of low muscle mass, low strength, and impaired performance are met.

Identifying these stages helps tailor treatment goals and monitor progression in both clinical practice and research settings.^[1]

SARCOPENIA AND RELATED SYNDROMES

Sarcopenia is a condition that is frequently correlated with other muscle atrophy symptoms. Being able to make distinctions between these will ensure not only targeted interventions but also age-related mechanism comprehension.^[1]

MANAGEMENT AND TREATMENT OF SARCOPENIA

The International Clinical Practice Guidelines for Sarcopenia provides a comprehensive list of resistance-based training as an essential tactic for attaining greater muscle strength, skeletal muscle mass, and overall physical function for sarcopenic individuals.^[21] To date, no available pharmacological or behavioral treatment has been found to be similarly as effective as resistance training in completely reversing the muscle loss of sarcopenia.

The American College of Sports Medicine and the American Heart Association recommend resistance training at an intensity of 70–90% of one-repetition maximum on at least 2 non-consecutive days per week. This intensity is effective in promoting muscle hypertrophy and strength gains, even among frail older adults.^[28]

Resistance training in older individuals not only increases muscle strength by a lot but also brings quite a noticeable increase in muscle mass, about 5–10%. The proportional change in strength is because of the adaptation in the neurons of a motor unit path rather than actual growth in the muscle. What is more, the advantages of resistance training, with only one session per week, can be long-lasting, especially if maintained with as little as one session per week.^[29]

GAPS AND CONTROVERSIES IN THE LITERATURE

Despite the fact that sarcopenia is now recognized as a significant public health issue, there are still numerous unexplored elements and debates. The most important one is the lack of accepted uniform diagnostic criteria: differing definitions such as those put forth by AWGS and EWGSOP2 lead to divergent clinical practices and prevalence estimation processes.^[3] The syndrome is poorly studied in lower to middle-income countries such as Nigeria which diminishes the relevance of existing tools and interventions.^[13] It is unknown how sarcopenia interacts with many other conditions whether as a primary, secondary, or concurrent condition, and terminology such as sarcopenic obesity remains ill-defined.^[25] In addition, the differentiation of sarcopenia and its distinction from frailty remains debated.^[24]

Recommendations

To combat the escalating problem of sarcopenia, the following recommendations are proposed:

1. Improved awareness and training: Medical healthcare workers in low-resource settings which lack sufficient knowledge regarding sarcopenia need better training on how to identify and diagnose the syndrome to avoid under-treatment and malnourished elderly.

2. Encourage resistance training: Muscle strength and sarcopenia stagnation should be the main focus of resistance-based exercise programs. This exercise plays an essential role in slowing muscle function decline and maintaining the overall physical health of elderly people.

3. Use various methods: Management of sarcopenia should include a combination of physiotherapy, nutrition therapy, and geriatric medicine. Multidisciplinary working approaches will resolve the optimization issue for treatment methods and other comorbidities such as frailty and obesity.

CONCLUSION

Sarcopenia is a complex issue concerning elderly people as it goes beyond muscle mass, muscle strength, and function, to disability, falls, and mortality risk. Although it is rarely the case, new understanding of its mechanisms has provided stipulations, the criteria for diagnosis remain largely ineffective alongside appropriate action frameworks. It becomes necessary, considering the multifaceted rationale of sarcopenia, that all factors (physiology, nutrition, and even psychosocial support) are encapsulated at once to remediate it. With appropriate support, the impacts of sarcopenia can be mitigated by incorporating early screenings, optimizing nutrition, and resistance exercising.