The review looks at mouse studies where the growth hormone/IGF‑1 system is turned off, which makes the animals live longer but can hurt their muscle health. It shows that while less IGF‑1 may boost lifespan, it also speeds up muscle loss (sarcopenia), which is a big factor in aging and frailty. The authors stress that keeping muscles strong—mainly through resistance training—is still the best way to improve healthspan.

The gap between lifespan and healthspan is increasing globally, resulting in millions of individuals spending additional years burdened by frailty or disease. This disparity, paired with the increasingly aged populations of Western nations, poses a palpable predicament to public health and the economy. Deterioration of the skeletal muscle system is a key contributor to illness, loss of independence, and diminishing healthspan. Muscle quality correlates to longevity due to its significant role in metabolic homeostasis and autonomous mobility, reducing instances of adverse events such as falls and fractures. The age-related loss of muscle mass and function is termed sarcopenia, affecting older adults ubiquitously without intervention through regular resistance training. Although clinical manifestations of sarcopenia are well characterized, the molecular mechanisms underlying its pathogenesis remain incompletely understood, limiting the development of targeted, mechanism-based interventions. To identify interventions beyond exercise that delay sarcopenia, it is necessary to identify early onset physiological alterations defining this process. Genetically modified mouse models of accelerated or delayed aging offer valuable insight into the cellular mechanisms that drive or mitigate sarcopenia. The latter is often achieved by disrupting the somatotropic axis, as multiple models exist that either lack growth hormone (GH) production or a functional GH receptor (GHR) paired with a secondary deficiency in insulin like growth factor-1 (IGF-1), which reliably extends lifespan across various species. This review evaluates GH's paradoxical role in muscular maintenance and contrasts the skeletal muscle health of various murine models of aging in effort to better outline the molecular underpinnings of sarcopenia.