Figure 1. Late-life intermittent fasting improves cognitive and physiological abilities concurrent with multi-tissue protein persulfidation in a sex-dependent manner. 20-month old C57BL/6 mice were placed on 2.5-months of Every-Other-Day (EOD) fasting. During and at the end of this intermittent fasting period, performance in metabolic, musculoskeletal, and cognitive tests were measured. Male mice improved in these areas, while little to no improvement was observed in female mice. Mechanistic examination to changes in hydrogen sulfide-related biology triggered by the EOD fasting revealed augmented protein persulfidation in muscle, brain, liver, and kidney. The dotted line between the two outcomes suggests a connection between decreased frailty and augmented H2S production and signaling. Figure created with BioRender.com.