Senescing in a warming world; how heatwaves interact with ageing

We’ve all been feeling the heat recently, but do older individuals feel it more? The climate is warming, both in average temperatures but also increases in extremes of temperature and more frequent heatwaves. This means animals might more often experience temperatures close to their physiological limits, with critical consequences for human health, food production, biodiversity and conservation. Studies in humans and a few other animals suggest that the impact of extreme temperature increases with age. However, major gaps in understanding the interplay between age and heat stress remain; 1) the shape of the relationship across the lifespan, 2) whether there are sex differences in these relationships, 3) whether different traits respond in the same way and 4) what molecular mechanisms underpin these relationships. Whilst classically survival limits have been used to predict responses to thermal extremes, there is increasing focus on sublethal effects of extreme heat. For example, we tested 43 species of Drosophila fruit fly, finding substantial variation in survival and fertility thermal limits in young males. Intriguingly, in more than half the species, males permanently lost fertility at a much cooler temperatures than their lethal limits, which could have devastating consequences for populations. Using a meta-analysis of more than 300 species, we have now shown that higher temperatures reduce both lifespan and reproductive output, but reproduction is much more severely affected. However, in systematically mapping existing literature, we found that most studies did not test thermal limits, did not test acute shocks (simulating heatwaves), and did not allow testing of sex or age-specific effects. This illustrates that such sublethal thermal effects require more attention. To address these significant knowledge gaps, we propose to use Drosophila fruit flies, as they are a well-established model for understanding ageing and thermal biology. We have new evidence that heating D. melanogaster males to just below their thermal limit is more harmful to 6-week-old than 1-week-old males, both in terms of fertility and survival. We will extend this approach to assess how the pattern changes over the lifespan (a gradual decline or cliff edge), whether females show different patterns, and whether there are common patterns across fly species. Gene expression changes with age, so we will then use D. melanogaster to test whether the changes with age are due to misregulation of genes that usually protect cells under stress. We will then functionally test some genes that do show these patterns by manipulating their expression to alter the sex and age-related patterns previously observed. Finally, we will flip the question to assess the long-term consequences of experiencing a heatwave when young. We expect those that survive temperatures close to their thermal limit will show faster age-related declines in various functions. We will test their lifespan, reproductive output, climbing ability, immune function, gut function and cognition, all of which have been separately shown to decline with age and be affected by temperature. The information we generate could immediately be used to inform better demographic predictions of what will happen to populations after heatwaves. Because the genetic responses to temperature are well conserved across species, in the longer term this could better predict vulnerable populations or individuals and to design interventions (e.g. when to prioritize for cool refuges for people, designing livestock breeding for heat resilience).