Language
English
Publication Date
7-29-2025
Journal
Trends in Cell Biology
DOI
10.1016/j.tcb.2025.06.006
PMID
40738832
PMCID
PMC12453298
PubMedCentral® Posted Date
9-23-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
aging, autophagy, hematopoietic stem cells (HSCs), proteasome, protein homeostasis (proteostasis), translation control
Published Open-Access
yes
Recommended Citation
André Catic, "Lessons in Longevity From Blood Stem Cells Under Protein Stress" (2025). Huffington Center on Aging Staff Publications. 53.
https://digitalcommons.library.tmc.edu/aging_research/53