Restoring the FOXO1 geroprotective pathway via seno-resistant mesenchymal progenitor cells alleviates primate epididymal aging - PubMed
4 hours ago
- #epididymal aging
- #cell therapy
- #FOXO1
- Aging in the male reproductive system leads to declining fertility, with epididymal dysfunction being a key factor.
- Multimodal analysis in non-human primates identified epididymal aging phenotypes including epithelial senescence, chronic inflammation, fibrosis, and functional decline.
- Single-nucleus transcriptomics showed principal cells (PCs) as the most affected epithelial cell type, with FOXO1 downregulation in aging PCs.
- FOXO1 deficiency drives cellular senescence in human epididymal epithelial cells, with FOXO1-LHX1 axis being essential for counteracting senescence.
- Intervention with senescence-resistant mesenchymal progenitor cells or their exosomes mitigated epididymal aging and restored FOXO1 expression.
- The study highlights the FOXO1-LHX1 axis as a protective pathway against primate epididymal aging, offering potential therapeutic targets.