With ageing, there is a loss of adult stem cell function. However, there is no direct evidence that this has a causal role in ageing-related decline. We tested this using muscle-derived stem/progenitor cells (MDSPCs) in a murine progeria model. Here we show that MDSPCs from old and progeroid mice are defective in proliferation and multilineage differentiation. Intraperitoneal administration of MDSPCs, isolated from young wild-type mice, to progeroid mice confer significant lifespan and healthspan extension. The transplanted MDSPCs improve degenerative changes and vascularization in tissues where donor cells are not detected, suggesting that their therapeutic effect may be mediated by secreted factor(s). Indeed, young wild-type-MDSPCs rescue proliferation and differentiation defects of aged MDSPCs when co-cultured. These results establish that adult stem/progenitor cell dysfunction contributes to ageing-related degeneration and suggests a therapeutic potential of post-natal stem cells to extend health.
Bibliographical noteFunding Information:
We thank Ayse Baybars for technical assistance, Minakshi Poddar for performing western blot experiments, Vaishali Patil for maintaining the mouse colony, Alison Logar for assistance with flow cytometry and Dr. Bridget Deasy (University of Pittsburgh, Pittsburgh, PA) for sharing her expertise, methodology and established protocols in regards to the live-cell imaging (LCI) system. This work was supported in part by The Ellison Medical Foundation AG-NS-0303-05 and ES016114, AG033907-01A1, and AR051456 from the National Institutes of Health, the Henry J. Mankin Endowed Chair at the University of Pittsburgh, William F. and Jean W. Donaldson endowed chair at the Children’s Hospital of Pittsburgh. J.S.T. was supported by NIH post-doctoral fellowship F30 AG032816. The experiments were approved by the Institutional Animal Care and Use Committee of the University of Pittsburgh.