Transgenerational fitness effects of lifespan extension by dietary restriction inCaenorhabditis elegans

Dietary restriction increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here we investigated the effect of dietary restriction by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in C. elegans . We show that while TF robustly reduces mortality risk and improves late-life reproduction in the parental generation (P 0 ), it has a wide range of both positive and deleterious effects on future generations (F 1 -F 3 ). Remarkably, great-grandparental exposure to TF in early-life reduces fitness and increases mortality risk of F 3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of dietary restriction underscoring the need to consider fitness of future generations in pursuit of healthy ageing.