Fig. 3

Interconnections between metabolism, epigenetic modifications, and longevity in C. elegans. There are tight connections between nutritional status, metabolite availability, and epigenetic modifications that are changing gene expression leading to longevity. a When the nutritional status changes, metabolite availability changes too. These changes can affect the post-translational modifications on specific histones and therefore gene expression beneficial for lifespan extension. Altered gene expression can also influence the metabolite pool and induce longevity. b Specific examples of what is outlined in a Left: Upon caloric restriction, the histone deacetylase SIR-2.1 is upregulated leading to lower levels of acetylation, which has been shown to upregulate autophagy and extend lifespan. Furthermore, sirtuins have been shown to act together with AMPK, a main inducer of autophagy. Therefore, it is possible that the caloric restriction-induced SIR-2.1 activity leads to an increase in AMPK activity, upregulating autophagy resulting in longevity. Right: Impairment of the methyltransferase complex COMPASS in the germline reduces trimethylation of histone 3 lysine 4, which activates the transcription factor SBP-1/SREBP-1 in the intestine. SBP-1/SREBP-1 controls the expression of the fatty acid desaturase FAT-7 that increases the levels of monounsaturated fatty acids leading to longevity. Both examples illustrate how metabolic cues can induce longevity, either through caloric restriction lowering metabolite availability or by reduction of certain histone modifiers leading to increase in specific metabolites