Lessons in longevity from blood stem cells under protein stress.
Abstract
Blood stem cells are among the body's longest-living cells despite being highly vulnerable to proteotoxic damage, which accelerates their aging. To maintain protein homeostasis (proteostasis), hematopoietic stem cells (HSCs) employ mechanisms such as reduced translation rates, high chaperone activity, autophagy, and selective protein degradation. These strategies mitigate protein misfolding, maintain quiescence, and preserve regenerative potential. Disruptions in proteostasis can lead to the elimination of impaired HSCs through differentiation or apoptosis, ensuring the integrity of the stem cell pool. Due to the systemic impact of the blood on aging and its experimental and clinical accessibility, investigating HSC proteostasis provides insights into longevity and potential therapeutic strategies. This review examines emerging mechanistic links between proteostasis and HSC fate, concluding with unresolved questions and challenges of the current research.
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Research summary
Hematopoietic stem cells utilize proteostasis mechanisms to mitigate aging-related damage and maintain their regenerative potential. The paper is relevant as it explores fundamental mechanisms of aging and longevity through the lens of stem cell biology, addressing root causes of aging rather than merely treating symptoms.
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