CD133 + endothelial-like stem cells restore neovascularization and promote longevity in progeroid and naturally aged mice

• Published in: Nature aging Vol. 3; no. 11; pp. 1401 - 1414
• Main Authors: Sun, Shimin, Meng, Yuan, Li, Mingying, Tang, Xiaolong, Hu, Wenjing, Wu, Weiwei, Li, Guo, Pang, Qiuxiang, Wang, Wengong, Liu, Baohua
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.11.2023
• Subjects: Aging; Animals; Endothelial Progenitor Cells - pathology; Longevity; Mice; Neovascularization, Pathologic - pathology; Stem cells; Stem Cells - pathology
• ISSN: 2662-8465; 2662-8465
• DOI: 10.1038/s43587-023-00512-z

The stem cell theory of aging dictates that a decline in the number and/or function of stem cells causes tissue degeneration and aging; however, it still lacks unequivocal experimental support. Here, using lineage tracing and single-cell transcriptomics, we identify a population of CD133 bone marrow-derived endothelial-like cells (ELCs) as potential endothelial progenitor cells, which contribute to tubular structures in vitro and neovascularization in vivo. We demonstrate that supplementation with wild-type and young ELCs respectively restores neovascularization and extends lifespan in progeric and naturally aged mice. Mechanistically, we identify an upregulation of farnesyl diphosphate synthase (FDPS) in aged CD133 ELCs-a key enzyme in isoprenoid biosynthesis. Overexpression of FDPS compromises the neovascularization capacity of CD133 ELCs, whereas FDPS inhibition by pamidronate enhances neovascularization, improves health measures and extends lifespan in aged mice. These findings highlight stem cell-based strategies for the treatment of progeria and age-related pathologies.