Dietary lithium chloride at concentrations of 10-25 mM reduced survival in male fruit flies, with unmated males experiencing the greatest mortality while frequently-mated males remained relatively protected. This mating-dependent interaction reveals that reproductive status fundamentally alters lithium's biological effects. The contradiction of previous research claiming lifespan extension highlights a critical gap in geroprotector research: the overlooking of reproductive context. This finding exposes how environmental factors can completely reverse a compound's effects, transforming a supposed life-extender into a survival liability. For human longevity research, this underscores the complexity of translating interventions across species and conditions. While lithium has shown promise in some studies for neuroprotection and mood stabilization in humans, this work suggests that individual physiological states—potentially including sexual activity, stress levels, or metabolic demands—may dramatically influence outcomes. The study represents an important negative result that challenges the field's assumptions about universal geroprotectors. Rather than paradigm-shifting, it's a necessary corrective that emphasizes context-dependent drug effects and the need for more nuanced approaches to longevity interventions.