Conserved across a majority of mammalian species, sarcopenia is the age-related loss of skeletal muscle mass and function, which is strongly predictive of mortality (1). Sarcopenic prevalence ranges between 10% and 40% of older adults dependent on the definition criteria; definitions including measures of muscle function in addition to muscle mass provide lower estimates of sarcopenia (2, 3). Despite ongoing updates to the clinical definition of sarcopenia (4), in preclinical rodent models, sarcopenia is usually designated by mouse or rat age or based only on muscle mass loss. During aging, the decline in muscle function exceeds deficits in muscle mass, underscoring the importance of functional assessment when defining sarcopenia. Given the importance of strength and function maintenance to mitigate age-related falls and injuries (5), several groups have successfully established preclinical frailty scoring criteria in C57BL/6 mice (6, 7). While compelling and discriminatory, these assessments are relatively burdensome in their assessment, requiring the longitudinal (or cross-sectional) assessment of a barrage of functional tests, including grip strength, inverted cling, treadmill, rotarod, and in vitro or in vivo muscle contractility. In this issue of the JCI, Kerr and colleagues provided a streamlined, clinically relevant definition of sarcopenia in aged (23–30 month old) C57BL/6J mice: at least two standard deviations below the mean of a young mouse reference group (4–9 month old) in measures of muscle mass, grip strength, and treadmill running time (8). Authors defined probable sarcopenia as exhibiting one deficit and sarcopenia as showing deficits in at least two out of the three criteria (8). Using their assessment, the authors determined the prevalence of sarcopenia to be approximately 20% in both 23–26 month old male mice and 27–28 month old female mice (8), comparable to the prevalence of sarcopenia is similarly aged humans (over 60 years old) (2, 3). Thus, this streamlined, clinically relevant protocol to classify sarcopenia phenotypes is feasible and reliable, enabling the improvement of sarcopenia-related animal studies beyond the common, age-alone designation, which is problematic given the approximately 20% prevalence observed in aged mice.

Preclinical rodent models provide a robust space to interrogate molecular mechanisms underlying sarcopenia. Taken together, prior literature has revealed multifactorial age-related alterations across pathways associated with loss of mitochondrial function, declines in anabolic factors (e.g., growth factors), elevated incidence of denervation, and increased inflammation in skeletal muscle (9–11). Abundant transcriptomic and proteomic changes have been identified across the lifespan, yet meaningful insight into sarcopenia has been limited with no consideration of muscle mass or function (9-11). The incorporation of a sarcopenic designation within the molecular profiling of aged muscle offers an important advancement to begin prioritizing putative therapeutic targets (8). As a further step, the inclusion of both male and female mice provided substantive advancement from prior work that was limited to male-only results (9-11), revealing a greater protection in female mice against declines in mitochondrial content and induction of protein catabolism (8).