Sarcopenia, derived from the Greek words for "poverty of flesh," describes the progressive loss of skeletal muscle mass and function that accompanies aging. Originally conceptualized as an inevitable consequence of aging, sarcopenia is now recognized as a pathological condition with significant clinical implications. The condition is associated with falls, fractures, disability, and mortality, leading to its inclusion in the International Classification of Diseases (ICD-10) in 2016.

The relationship between muscle health and immune function has long been suspected but only recently subjected to rigorous investigation. Muscle serves not only as a motor organ but also as an endocrine tissue, producing myokines that influence immune cell function and inflammatory responses. Additionally, muscle represents an important reservoir of amino acids that can be mobilized during physiological stress, including infection.

This prospective cohort study leveraged the UK Biobank, one of the largest and most comprehensively characterized population cohorts in the world, to examine the association between sarcopenia and infection risk. The study included 458,332 participants who were followed for a median of over a decade, during which time incident infections were ascertained through hospital records and death registries.

Sarcopenia was defined using appendicular lean mass adjusted for body size, measured by bioelectrical impedance analysis at baseline. Participants were categorized as having no sarcopenia, pre-sarcopenia (low muscle mass), or sarcopenia (low muscle mass plus low muscle strength or physical performance). This definition aligns with consensus criteria from international working groups on sarcopenia.

The key findings revealed a graded association between sarcopenia and infection risk. Compared to participants without sarcopenia, those with pre-sarcopenia had a moderately increased risk of infections, while those with sarcopenia had a substantially elevated risk. This association persisted after adjustment for potential confounders including age, sex, socioeconomic status, lifestyle factors, and comorbidities.

The association was observed across multiple infection types, including respiratory infections, urinary tract infections, skin and soft tissue infections, and sepsis. The strength of association varied by infection type, with particularly strong associations for respiratory infections and sepsis, suggesting that sarcopenia may have particular implications for severe infections requiring hospitalization.

Several biological mechanisms may underlie the observed association. First, muscle produces myokines such as interleukin-6 (in its anti-inflammatory form), interleukin-15, and irisin, which influence immune cell function and inflammatory responses. Reduced muscle mass may impair this endocrine function, compromising immune defense. Second, muscle serves as a reservoir of amino acids, particularly glutamine, that are critical for immune cell proliferation and function during infection. Third, sarcopenia is associated with chronic low-grade inflammation, which may impair adaptive immune responses.

The public health implications of these findings are substantial given the aging global population and the high prevalence of sarcopenia among older adults. Preventing or treating sarcopenia through exercise, nutrition, and potentially pharmacological interventions could reduce infection risk and associated healthcare costs. The COVID-19 pandemic has further highlighted the importance of understanding and addressing risk factors for infectious disease susceptibility.

Several limitations should be acknowledged. Sarcopenia was assessed at a single time point, and changes in muscle mass over time were not captured. Residual confounding by unmeasured factors cannot be excluded. The study population was predominantly of European ancestry, limiting generalizability to other populations.

Future research directions include investigation of the mechanisms linking muscle health and immune function, evaluation of whether sarcopenia interventions reduce infection risk, and exploration of gene-environment interactions that may modify the sarcopenia-infection relationship.
DOI
10.1007/s11684-026-1224-0