Single-Cell Multi-Omics Uncovers the Role of Microbiota-Derived Metabolites in Shaping the Epigenetic Landscape of Neural Stem Cells during Aging
DOI:
https://doi.org/10.55006/Keywords:
Epigenetic modulators, Neural stem cells, Gene expression, Single-cell transcriptomics, EpigenomicsAbstract
Aging is a multifactorial process characterized by systemic physiological decline, during which neural stem cells (NSCs) undergo epigenetic reprogramming, contributing to cognitive impairment. Emerging evidence implicates the gut-brain axis in modulating this decline, yet the mechanistic underpinnings remain elusive. Here, we integrate single-cell transcriptomics and epigenomics (scRNA-seq and scATAC-seq) to dissect how microbiota-derived short-chain fatty acids (SCFAs) influence the chromatin accessibility and gene expression patterns of NSCs across age groups in murine models. SCFA supplementation in aged mice restores youthful epigenetic states in a subset of NSCs, promotes neurogenesis-associated transcriptional programs, and reduces senescence signatures. These findings uncover a novel avenue where microbiota metabolites serve as epigenetic modulators of neural aging, offering targets for therapeutic rejuvenation of the aging brain.
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Copyright (c) 2026 Mustapha Abdulsalam, Ojeba Innocent Musa, Miracle Uwa Livinus, Amosa Sulyman Olayinka, Adewale Opeyemi Ajibola, Maryam Ibrahim Aminu, Imam Muzeenat Oyinkansola
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