Senescent-associated β-galactosidase accumulation does not correlate with lifespan in different strains of <i>Nothobranchius furzeri</i> but does respond to intermittent fasting to extend lifespan.

Senescent cell (SC) accumulation theoretically causes aging-related tissue malfunction. We examined SC burden in short-lived and long-lived <i>Nothobranchius furzeri</i> fish strains, and fasting's effects on SCs. Despite different lifespans, SC accumulation rates didn't correspond between strains. The long-lived strain showed sex-based lifespan differences without SC burden differences. A 14-day fast reduced SC burden in short-lived fish, but this effect was temporary. Fasting extended median lifespan without affecting maximum lifespan, suggesting transient healthspan(definition) improvement. We conclude that saβgal-assessed SC burden doesn't necessarily correspond with lifespan between strains but may within strains. Our findings confirm intermittent fasting improves health and median lifespan.