Effects of low-dose sildenafil on survival and age-associated phenotypes in the African turquoise killifish

Abstract Sildenafil, a phosphodiesterase type 5 inhibitor, is clinically used for vascular disorders, but its potential role in vertebrate aging remains incompletely understood. In this study, we evaluated the effects of sildenafil on lifespan-associated phenotypes using the African turquoise killifish, a short-lived vertebrate model suitable for aging research. Sildenafil was orally administered once weekly at doses of 5 or 30 mg/kg to sex-balanced GRZ killifish after sexual maturation. Survival was monitored daily, while body length, body weight, and locomotor activity were assessed longitudinally. In the result, 5 mg/kg sildenafil delayed the initiation of death from 63 days in controls to 93 days and modestly increased median lifespan from 121.5 to 126 days. Maximum lifespan was also increased from 186 to 204 days. In contrast, 30 mg/kg sildenafil delayed the first death but did not improve median or maximum lifespan. Growth changes were broadly comparable among groups, suggesting that sildenafil did not markedly impair somatic growth. Locomotor activity declined with age across groups, while treatment-associated differences require further validation. These findings suggest that low-dose sildenafil may delay early mortality and modestly improve lifespan parameters in African turquoise killifish, supporting further investigation of phosphodiesterase signaling as a potential modulator of vertebrate aging.