In mouse models that mimic human muscle atrophy in the context of different diseases and conditions, such as denervation, cachexia (Box 1), starvation or sepsis, FOXO3 and FOXO4 upregulate macroautophagy and youth optimizer (MYTHO; also known as PHAF1), a newly identified regulator of muscle autophagy, to drive autophagic processes and promote muscle atrophy (Leduc-Gaudet et al., 2023). This evidence concerns the gene PHAF1 and Sepsis.