Blood stem cells can be rejuvenated several ways

Blood stem cells (hematopoietic stem cells, HSCs) produce all the cells of the immune system. With age, they function less effectively: self-renewal declines, incorrect cell types are produced more often, and small cell clones begin to dominate. This affects resistance to infection and the pace of systemic aging. A review article summarizes which rejuvenation strategies the researchers consider most promising.

Exercise improves overall health but has little direct impact on the stem cells themselves. Dietary restriction and pharmacological agents targeting the same cellular energy sensors show greater effects. Nicotinamide riboside (NR), a precursor to NAD+, restores energy metabolism in aged stem cells. Inhibition of mTOR, a protein that regulates cell growth, via rapamycin improves self-renewal and antiviral immunity in old mice.

Enzymes and reprogramming

Two enzymes, SIRT3 and SIRT7, influence how stem cells age. Lower SIRT3 levels impair self-renewal; higher levels improve it. SIRT7 keeps the balance of cell types a stem cell produces in check. When SIRT7 is lost, stem cells become exhausted. Overexpression partially reverses those aging features, at least in mouse models. Another approach, transient activation of so-called Yamanaka factors, temporarily returns cells to a younger state and extended lifespan in animal studies. Whether these findings translate to humans has not yet been demonstrated.

A broad landscape of approaches

The review makes clear that no single method is sufficient on its own. Each approach targets a different aspect of stem cell aging, energy metabolism, cell identity, or the immediate environment of the stem cell (the niche). From a longevity standpoint, it is notable that multiple mechanisms appear targetable simultaneously, but combination therapies in humans remain largely unexplored.

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