Although previous studies employing FoxO1/3/4 triple-knockout and Atrogin-1-deficient cells have established the critical role of the FoxO3–Atrogin-1/MuRF-1 axis in acute muscle atrophy (Zhao et al., 2007; Milan et al., 2015), its causal relevance in naturally occurring chronic sarcopenia remains undefined. The gene discussed is FOXO1; the disease is sarcopenia.