Epigenetic alterations are a primary hallmark of ageing. In mammals, age-related epigenetic changes alter gene expression profiles, disrupt cellular homeostasis and physiological functions and, therefore, promote ageing. It remains unclear whether ageing is also driven by epigenetic mechanisms in invertebrates. Here, we used a pharmacological hypomethylating agent (RG108) to evaluate the effects of DNA methylation (DNAme) on lifespan in an insect-the bumblebee Bombus terrestris. RG108 extended mean lifespan by 43% and induced the differential methylation of genes involved in hallmarks of ageing, including DNA damage repair and chromatin organization. Furthermore, the longevity gene sirt1 was overexpressed following the treatment. Functional experiments demonstrated that SIRT1 protein activity was positively associated with lifespan. Overall, our study indicates that epigenetic mechanisms are conserved regulators of lifespan in both vertebrates and invertebrates and provides new insights into how DNAme is involved in the ageing process in insects.
RG108 for the ITP?
Also, Bombus terrestris is a very promising model organism for longevity research. What epigenetic differences are underlying the lifespan difference between queens and workers?
Social Hymenoptera (i.e. ants, social bees and social wasps) are particularly useful models for studying the epigenetic regulation of ageing because the same genetic background can lead to phenotypically distinct groups with contrasting lifespans. The female castes—reproductive queens and non-reproductive workers—provide a dramatic illustration of this point. Queens and workers of social Hymenoptera exhibit the largest intraspecific difference in lifespan ever observed in animals. For instance, in some ant species, queens may live for more than 20 years, while workers die after just a few months