Scientific Publications
Defining microbiota-derived metabolite butyrate as a senomorphic: therapeutic potential in the age-related T cell senescence.
Aging Cell, Aging Cell . 2025 Dec;24(12):e70257, Aging Cell . 2025 Dec;24(12):e70257
Advancing age is accompanied by an accumulation of senescent T cells that secrete pro-inflammatory Senescence-Associated Secretory Phenotype (SASP) molecules. Gut-microbiota-derived signals are increasingly recognised immunomodulators. In the current study, we demonstrate that ageing and the accumulation of senescent T cells is accompanied by a reduction in the microbial-derived short-chain fatty acid (SCFA) butyrate. Culturing aged T cells in the presence of butyrate supresses the induction of senescence phenotype and inhibits secretion of pro-inflammatory SASP factors such as IL6 and IL8. Administration of faecal supernatants from young mice rich in butyrate prevented in-vivo accumulation of senescent spleen cells in of aged mice. The molecular pathways governing butyrates senomorphic potential include reduced expression of DNA damage markers, lower mitochondria ROS accumulation and downregulation of m TOR activation which negatively regulates the transcription factor NF?B. Our findings establish butyrate as a potent senomorphic agent and provide the evidence base for future microbiome restitution intervention trials using butyrate supplements for combatting T cell senescence, reducing inflammation and combatting age-related pathologies; together extending life-long health.
Aging Cell, Aging Cell . 2025 Dec;24(12):e70257, Aging Cell . 2025 Dec;24(12):e70257
View Publication
