Our study revealed functional insights and a putative causality for the role of the gut–muscle axis in the mechanism of melatonin ameliorating age‐related sarcopenia, namely, inhibition of the LPS‐induced Tnfrsf12a/caspase‐8 signalling pathway or serum metabolites as intermediates in the gut–muscle axis. The gene discussed is TNFRSF12A; the disease is age.