Sarcopenia

Some loss of muscle and strength with age is universal. Sarcopenia refers to the point at which this loss becomes a disease in its own right, severe enough to make everyday tasks difficult, raise the risk of falls and threaten independence. The European Working Group on Sarcopenia in Older People first defined it in 2010 and revised the definition in its second consensus, EWGSOP2, which calls sarcopenia a muscle disease and places low muscle strength at its centre [1]. Sarcopenia has its own diagnosis code in the US version of the international disease classification, ICD-10-CM M62.84 [1].

EWGSOP2 distinguishes primary (age-related) sarcopenia, where no other cause is evident, from secondary sarcopenia, where a systemic disease, inactivity or poor nutrition contributes. It also separates acute sarcopenia, lasting less than 6 months and usually linked to an acute illness or injury, from chronic sarcopenia, lasting 6 months or more and more likely linked to progressive conditions [1].

Sarcopenia overlaps with, but differs from, frailty, a broader loss of physiological reserve across several body systems, and from malnutrition and cachexia, the rapid loss of muscle and weight driven by diseases such as cancer or organ failure. Low grip strength and slow walking speed are features of both sarcopenia and physical frailty [1].

EWGSOP2 uses a three-step algorithm. Low muscle strength, measured by grip strength or a chair-rise test, makes sarcopenia probable. Low muscle quantity or quality, measured by a DXA scan (a low-dose X-ray body scan), bioelectrical impedance, CT or MRI, confirms the diagnosis. Poor physical performance, such as a walking speed of 0.8 m per second or less, marks it as severe [1].

For case-finding, EWGSOP2 suggests the SARC-F questionnaire, a five-item self-report of limitations in strength, walking, rising from a chair, climbing stairs and falls [1]. The international ICFSR guideline advocates rapid screening with gait speed or SARC-F and conditionally recommends using an internationally accepted definition, such as the EWGSOP or FNIH criteria, for diagnosis [2].

Estimates of how common sarcopenia is vary widely with the definition, the measurement method and the population. The ICFSR guideline puts it at approximately 6% to 22% of older adults [2]. Studies cover very different settings, from older adults living in the community to outpatients, hospital inpatients and nursing-home residents, and pooled analyses therefore report results separately by setting [3].

Muscle mass declines from middle age, and at age 75 longitudinal studies report losses of 0.80% to 0.98% a year in men and 0.64% to 0.70% a year in women. Strength falls faster, at about 3% to 4% a year in men and 2.5% to 3% a year in women at the same age [6]. The faster loss of strength reflects declining muscle quality as well as quantity.

Anabolic resistance, a reduced muscle protein synthesis response to dietary protein, is one mechanism; it is the basis of expert recommendations for higher protein intakes after 65 [7]. Physical inactivity, including periods of bed rest during illness, accelerates muscle loss. EWGSOP2 lists disease, inactivity and poor nutrition as the main contributors to secondary sarcopenia [1]. Changes in the motor nerves that drive muscle fibres and in hormones are also studied as contributors, and the mix of causes differs between individuals.

Chronic low-grade inflammation with age, termed inflammageing, is listed as a risk factor for sarcopenia. Mechanistic studies suggest inflammation promotes muscle catabolism and interferes with growth-factor signalling, but this requires confirmation in humans, and whether reducing inflammation benefits non-cardiovascular conditions such as sarcopenia remains controversial [8].

A 2022 systematic review and meta-analysis included 56 studies (42,108 participants, mean ages from 49 to 87 years) of community-dwelling adults, outpatients, hospital inpatients and nursing-home residents [3]. Sarcopenia was associated with a hazard ratio (the risk in one group relative to another) of 2.00 (95% CI 1.71 to 2.34) for death, and an odds ratio of 2.35 (95% CI 1.64 to 3.37). The association held regardless of population, sarcopenia definition and length of follow-up.

An earlier meta-analysis of 17 prospective studies using the original European definition found sarcopenia associated with a pooled odds ratio of 3.60 (95% CI 2.96 to 4.37) for death, higher in people aged 79 or older, and 3.03 (95% CI 1.80 to 5.12) for functional decline [4]. Both studies that examined falls found more falls in people with sarcopenia; results for fractures and length of hospital stay were mixed. Measures that reduce falls are described in fall prevention.

The International Conference on Sarcopenia and Frailty Research (ICFSR) guideline, graded with the GRADE method, strongly recommends resistance-based physical activity as treatment for sarcopenia and conditionally recommends protein supplementation or a protein-rich diet. It gives no recommendation for vitamin D or anabolic hormones and found the evidence too limited to assess other treatments, including medicines in development [2].

Trials in adults aged 50 and over show that resistance training increases strength by about 24% to 33% on standard lifts [9] and lean body mass by about 1.1 kg on average, with larger gains from higher-volume programmes and smaller gains at older ages [5]. For older adults, the WHO recommends varied multicomponent physical activity emphasising functional balance and strength training on 3 or more days a week to improve function and prevent falls [10]. Related programmes are described in balance training and functional fitness.

For people over 65, the PROT-AGE expert group recommended at least 1.0 to 1.2 g of protein per kg of body weight a day, at least 1.2 g for active people, and 1.2 to 1.5 g for most people with acute or chronic illness, with severe kidney disease not on dialysis as an exception [7].

The links between sarcopenia and death are observational. Sarcopenia is often a consequence of underlying disease as well as a possible cause of harm: a person with advanced heart or lung disease may be both weak and at higher risk of dying from that disease. The studies therefore do not show how much risk would be removed by reversing muscle loss.

Differences in definitions also complicate comparisons. The original and revised European definitions, the Asian (AWGS), FNIH and other criteria use different tests and cut-offs [3], and prevalence estimates range several-fold as a result [2]. Most treatment trials measure strength, muscle mass or physical performance rather than falls, disability or survival.