Catic André
Department of Molecular and Cellular Biology, Huffington Center on Aging, Stem Cells and Regenerative Medicine Center, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Trends Cell Biol. 2025 Jul 29. doi: 10.1016/j.tcb.2025.06.006.
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.
尽管血液干细胞极易受到蛋白质毒性损伤（这种损伤会加速其衰老），但它们却是人体中寿命最长的细胞之一。为维持蛋白质稳态（蛋白质平衡），造血干细胞采用降低翻译速率、提高伴侣蛋白活性、自噬和选择性蛋白质降解等机制。这些策略可减轻蛋白质错误折叠、维持静止状态并保留再生潜力。蛋白质稳态的破坏可导致受损的造血干细胞通过分化或凋亡被清除，从而确保干细胞库的完整性。由于血液对衰老具有全身性影响，且具有实验和临床可及性，因此研究造血干细胞的蛋白质稳态有助于深入了解长寿和潜在的治疗策略。本综述探讨了蛋白质稳态与造血干细胞命运之间新出现的机制联系，并以当前研究中未解决的问题和挑战作为结尾。
