Epigenetic modifications impact metabolite production and lifespan in yeast

Abstract

Epigenetics have been shown to play a crucial role in regulating gene expression during the aging and immune response processes, with changes in epigenetic marks being linked to age-related diseases and inflammatory responses. Recently it has been revealed that S-adenosyl-l-homocysteine can extend the lifespan of the budding yeast Saccharomyces cerevisiae by mimicking caloric restriction. In this present study, we aimed to activate the production of S-adenosyl-l-homocysteine by S. cerevisiae through introducing epigenetic changes as a result of exposure to benzoic acid, a known epigenetic modifier. The impact of this on metabolite production was evaluated using LC-MS/MS. The study successfully activated and measured an overproduction of S-adenosyl-l-homocysteine (SAH) in yeast previously exposed to benzoic acid and led to lifespan extension. The link between the aging process and immune responses in yeast was further explored in the study. The production of SAH was downregulated while several inflammatory response metabolites were upregulated in aging cells. The upregulation of inflammatory response metabolites with their inherent anti-viral and antimicrobial activities could potentially be valuable for use in human health applications. By contrast, in cells with higher lifespans these inflammatory metabolites were downregulated. This finding supports the concept that aging leads to higher levels of histone methylation and acetylation, which in turn cause the production of immune response metabolites and inflammation. By contrast, it appears that lower levels of histone methylation and acetylation as seen in healthy cells, can increase production of metabolites responsible for lifespan extension, such as SAH. In summary, this study provides insights into the molecular mechanisms involved in lifespan extension and the role of metabolites in regulating aging in yeast. The research sheds light on the interplay between metabolism, epigenetics, immunity and aging and contributes to the growing field of metabolomics.