Abstract
AbstractThe 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.
Funder
National Natural Science Foundation of China
Ministry of Science and Technology of the People’s Republic of China
Guangdong Science and Technology Department
Shenzhen Science and Technology Innovation Commission
Publisher
Springer Science and Business Media LLC
Subject
Neuroscience (miscellaneous),Geriatrics and Gerontology,Aging
Reference51 articles.
1. Le Couteur, D. G. & Lakatta, E. G. A vascular theory of aging. J. Gerontol. A 65, 1025–1027 (2010).
2. Vas, V., Hajdu, M., Paloczi, K. & Uher, F. Alternative views of tissue stem cell plasticity. Haematologia 32, 175–190 (2002).
3. Barker, N., Bartfeld, S. & Clevers, H. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell 7, 656–670 (2010).
4. Yu, V. W. C. & Scadden, D. T. Hematopoietic stem cell and its bone marrow niche. Curr. Top. Dev. Biol. 118, 21–44 (2016).
5. Beauséjour, C. in Handbook of Experimental Pharmacology (ed. Michel, M. C.) 67–88 (Springer, 2007).
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献