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In this review, we will discuss the potential link between Sestrins, stem cells, and ageing.Hematopoietic stem cells (HSCs) are characterized by two key features Self-renewal ability and multilineage differentiation potential (multipotentiality). With aging, these key features gradually change. This is thought to be related to hematological diseases. However, clonal in vivo analysis assessing the potential of HSCs to differentiate along erythroid and platelet lineages ("five-lineage tracing" has not been performed in the aged bone marr