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The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Defining Microbiota‐Derived Metabolite Butyrate as a Senomorphic: Therapeutic Potential in the Age‐Related T Cell Senescence

Rees, Nia Paddison, Conway, Jessica, Dugan, Ben, Amir, Sayeda S., Parker, Aimee, Carding, Simon R., Duggal, Niharika A.·2025·Aging Cell
DOI 10.1111/acel.70257PMC PMC12686592
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Abstract

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 as immunomodulators. In the current study, we demonstrated that ageing and the accumulation of senescent T cells are accompanied by a reduction in microbial‐derived short‐chain fatty acids (SCFAs). Culturing aged T cells in the presence of butyrate suppresses the induction of a senescence phenotype and inhibits the 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 aged mice. The molecular pathways governing butyrate's senomorphic potential include a reduced expression of DNA damage markers, lower mitochondrial ROS accumulation, and downregulation of mTOR activation, which negatively regulates the transcription factor NFκB. Our findings establish butyrate as a potent senomorphic agent and provide the evidence base for future microbiome restitution intervention trials using butyrate supplements for combating T cell senescence, ultimately reducing inflammation and combating age‐related pathologies to extend lifelong health.

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  • Butyrate suppresses NF-κB activation and downregulates mTOR signaling, reducing pro-inflammatory SASP cytokine secretion by approximately 40-50% in aged T cells in vitro.

    “butyrate suppresses NF-κB activation and downregulates mTOR signaling, thereby reducing pro-inflammatory SASP cytokine secretion (e.g., IL-6, IL-8, and IL-1β) by approximately 40–50% in aged T cells in vitro100.”

    From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [100]

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Research works printed but not linked: 35

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Metadata

Authors
Rees, N. P., Conway, J., Dugan, B., Amir, S. S., Parker, A., Carding, S. R., & Duggal, N. A.
Venue
Aging Cell
Publisher
Wiley
Published
2025-11-07
Volume
24
Issue
12
ISSN
  • 1474-9718
  • 1474-9726
DOI
10.1111/acel.70257
PMC
PMC12686592
Cited by
16
References
10
Language
en
Licence

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