Abstract
Dietary restriction (DR) 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 DR by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in Caenorhabditis elegans. We show that while TF robustly reduces mortality risk and improves late-life reproduction of the individuals subject to TF (P0), it has a wide range of both positive and negative effects on their descendants (F1–F3). Remarkably, great-grandparental exposure to TF in early life reduces fitness and increases mortality risk of F3 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 DR, underscoring the need to consider fitness of future generations in pursuit of healthy ageing.
Highlights
Dietary restriction (DR), a reduction in nutrient intake without malnutrition, is an environmental intervention that robustly extends lifespan and/or improves health across a broad cross-taxonomic variety of organisms from yeast to mice to primates [1,2,3,4,5]
We focused on addressing the following unresolved questions. (i) How does DR by temporary fasting (TF) affect mortality risk and reproductive ageing once the animals return to their standard food regime? (ii) How do offspring of TF parents perform in matching and mis-matching environments? (iii) Do transgenerational effects of ancestral fasting shape mortality risk and reproductive ageing of more distant descendants? (iv) Does reduced reproduction under DR represent a response mediated by odour perception? 2 We use C. elegans nematode worms, which are an established model for the study of both DR and transgenerational effects, to investigate how 2-day bacterial deprivation in early adulthood affects mortality risk and age-specific reproduction in ancestors and their descendants over a total of four generations
We found evidence of several negative transgenerational effects of DR by TF in P0 on the mortality and fitness of individuals from the F3 generation
Summary
Dietary restriction (DR), a reduction in nutrient intake without malnutrition, is an environmental intervention that robustly extends lifespan and/or improves health across a broad cross-taxonomic variety of organisms from yeast to mice to primates [1,2,3,4,5]. 2 We use C. elegans nematode worms, which are an established model for the study of both DR and transgenerational effects, to investigate how 2-day bacterial deprivation in early adulthood affects mortality risk and age-specific reproduction in ancestors and their descendants over a total of four generations. To study the transgenerational effects of P0 diet treatments, individual late-L4 stage nematodes were randomly exposed to one of four dietary treatments (figure 1a; sample sizes varied for each treatment owing to disproportionate day 1 and two mortality of TF individuals by walling (n = 110 for AL/AL(FO), n = 191 for FO, n = 259 for TF) They remained exposed to these dietary conditions for 2 days prior to transfer onto standard ad libitum control plates seeded with E. coli. N.B. (FO) represents the presence of a food odour layer. (Online version in colour.)
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