Mobilization‐based transplantation of young‐donor hematopoietic stem cells extends lifespan in mice

• Published in: Aging cell 2020-03, Vol.19 (3), p.e13110-n/a
• Main Authors: Guderyon, Michael J., Chen, Cang, Bhattacharjee, Anindita, Ge, Guo, Fernandez, Roman A., Gelfond, Jonathan A. L., Gorena, Karla M., Cheng, Catherine J., Li, Yang, Nelson, James F., Strong, Randy J., Hornsby, Peter J., Clark, Robert A., Li, Senlin
• Format: Article
• Language: English
• Subjects: Age Factors; age‐associated health deficit; Aging; Animals; Body Weight; Bone marrow; Bone Marrow - physiology; Bone marrow transplantation; Cell therapy; Cellular Senescence; Eating; Female; Food intake; Frailty - blood; Frailty - therapy; Genotype; Health aspects; hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Life span; Longevity; Mice; Mice, Inbred C57BL; mobilization‐based conditioning; Morbidity; mouse; Original Paper; Original Papers; Phenotype; Phenotypes; Regeneration; Stem cell transplantation; Stem cells; Stroma; Tissue Donors; Transplant Recipients; Transplantation
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.13110

Mammalian aging is associated with reduced tissue regeneration and loss of physiological integrity. With age, stem cells diminish in their ability to regenerate adult tissues, likely contributing to age‐related morbidity. Thus, we replaced aged hematopoietic stem cells (HSCs) with young‐donor HSCs using a novel mobilization‐enabled hematopoietic stem cell transplantation (HSCT) technology as an alternative to the highly toxic conditioning regimens used in conventional HSCT. Using this approach, we are the first to report an increase in median lifespan (12%) and a decrease in overall mortality hazard (HR: 0.42, CI: 0.273–0.638) in aged mice following transplantation of young‐donor HSCs. The increase in longevity was accompanied by reductions of frailty measures and increases in food intake and body weight of aged recipients. Young‐donor HSCs not only preserved youthful function within the aged bone marrow stroma, but also at least partially ameliorated dysfunctional hematopoietic phenotypes of aged recipients. This compelling evidence that mammalian health and lifespan can be extended through stem cell therapy adds a new category to the very limited list of successful anti‐aging/life‐extending interventions. Our findings have implications for further development of stem cell therapies for increasing health and lifespan. Aged recipient mice underwent a mobilization‐based hematopoietic stem cell transplantation procedure followed by infusion of young‐donor stem cells. Young‐donor stem cells reverse age‐associated features and increase the health and longevity of aged recipients following aged hematopoietic stem cell replacement. Further, young‐donor cells maintained youthful features while under the influence of the aged bone marrow stroma.