Gut microbiota-epigenetic interactions in systemic aging: mechanistic drivers for endocrine and reproductive network remodeling and therapeutic modulation
Abstract
Researchers now see aging as a process shaped by the interactions among metabolism, epigenetics, and hormones. Recent studies suggest that gut microbes play an important role in this system by making metabolites that can affect gene expression and chromatin structure. Still, it is not fully clear how gut microbes and the body influence each other as we age, since both are constantly changing. This review brings together current research on how metabolites from gut microbes-such as short-chain fatty acids, bile acids, tryptophan derivatives, and polyamines-affect the body's epigenetic machinery through processes such as DNA methylation, histone modifications, and chromatin remodeling. We examine evidence from cell studies, animal experiments, and human research to assess the strength of the links and distinguish direct effects on chromatin from indirect metabolic or gene-expression changes. We focus especially on endocrine and reproductive organs, such as the hypothalamus, pancreas, liver, fat tissue, and cells that support the gonads, where signals from gut microbes overlap with hormonal control and metabolism. In these tissues, microbial metabolites influence key pathways related to inflammation, mitochondria, and nutrient sensing, but there is still little direct evidence in humans. The review also points out differences between lab models and what is observed in patients, highlighting the need for further work to apply these findings in real-world settings. Interactions…
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