Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice

Abstract Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit “younger” molecular profiles and functions, marked by low levels of CD150 expression. Mechanistically, CD150 low HSCs from old mice can effectively differentiate into downstream lineage cells but not their CD150 high counterparts. Notably, transplantation of old CD150 low HSCs attenuates aging phenotypes and prolongs lifespan of elderly mice compared to those transplanted with unselected or CD150 high HSCs. Importantly, reducing the dysfunctional CD150 high HSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of “younger” HSCs in old mice, and aging-associated functional decline can be mitigated by reducing dysfunctional HSCs.