Aging-associated changes in the function of the immune system are referred to as senescent immune remodeling (SIR). Here we review the current understanding on the cellular and molecular mechanisms underlying SIR. We focus on aging-associated changes in T and B cells, and discuss recent evidence supporting the notion that aging of the hematopoietic stem cell (HSC) compartment directly contributes to SIR due to aging-associated alterations in stem cell differentiation. We conclude by outlining strategies to attenuate SIR, including approaches to rejuvenate HSCs, which may open new avenues for targeting SIR in the clinic.
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