Reassessment of Hematopoietic Stem Cell Aging through Metabolic Uncoupling and Mitochondrial Resilience.

Chong Yang, Keiyo Takubo, Toshio Suda

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, China; Tianjin Institutes of Health Science, China. · pubmed

Paper

Abstract

Hematopoietic stem cell (HSC) aging is often described as a gradual loss of stem cell fitness that culminates in impaired blood production, immune dysfunction, and increased susceptibility to hematologic disease. However, recent work suggests that this view is too simple. Rather than a uniform decline, aging appears to remodel the HSC compartment into metabolically and functionally distinct states, including maladaptive trajectories as well as surprisingly resilient subsets. In this review, we argue that HSC aging is best understood through the interplay of mitochondrial regulation, metabolic uncoupling, and niche-derived stress, with particular emphasis on how recent findings revise several longstanding assumptions in the field (Box 1).

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

This review proposes that metabolic uncoupling and mitochondrial resilience are key mechanisms driving heterogeneous aging trajectories in hematopoietic stem cells, challenging the uniform decline model. The paper is relevant as it addresses fundamental cellular aging mechanisms in stem cells, which are central to longevity research, but as a review article offering a conceptual framework rather than novel experimental data, its direct scientific impact is limited to synthesizing existing knowledge.

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