Abstract
Pharmacological modulation of ageing is viewed as a viable route to extending lifespan and healthspan, yet the efficacy of putative geroprotectors may depend strongly on physiological and environmental context. Lithium chloride (LiCl) has been reported to extend lifespan in several model organisms, but evidence remains inconsistent and the role of reproductive investment—an energetically costly and often lifespan-correlated process—has rarely been examined. We tested the effects of dietary LiCl on survival and reproductive performance in male Drosophila melanogaster , comparing unmated (UM) and frequently-mated (FM) males. Contrary to previous work, both a concentration previously reported as beneficial (25 mM), and a lower concentration (10 mM) reduced survival, with effects driven exclusively by UM males. FM males were comparatively protected, revealing a strong mating-dependent interaction. LiCl had no detectable effect on male late-life mating latency, sterility, or paternity share, but reduced some post-copulatory performance in FM males by increasing female remating, indicating that somatic and reproductive responses to LiCl can be decoupled. These results demonstrate that lithium’s effects on survival are strongly dependent on reproductive environment, highlighting the importance of reproductive context when evaluating its impact on lifespan.