bims-mithem Biomed News
on Mitochondria in Hematopoiesis
Issue of 2026–01–18
eight papers selected by
Tim van Tienhoven, Erasmus Medical Center
  1. Aging of the Hematopoietic System: Mechanisms, Consequences, and Systemic Interactions.
  2. [Dysfunction and premature aging of hematopoietic stem cells in Down syndrome].
  3. An inflammatory and quiescent HSC subpopulation expands with age in humans.
  4. CCR5 marks a subset of mouse hematopoietic stem cells that are myeloid primed and expand with age.
  5. Iron oxide nanoparticles-driven mitochondrial renewal rejuvenates the aged bone marrow niche.
  6. Potassium ion homeostasis modulates mitochondrial function.
  7. Mitochondrial transfer in cancer: mechanisms, immune evasion, and therapeutic opportunities.
  8. Cellular Senescence, Inflammaging and Cardiovascular Disease.
  1. Aging Cell. 2026 Feb;25(2): e70385
    Aging of the Hematopoietic System: Mechanisms, Consequences, and Systemic Interactions.
    Masashi Miyawaki, Seiji Hashimoto, Sumito Ogawa, Yoshitaka Kase.
      The aging of the hematopoietic system is central to physiological aging, with profound consequences for immune competence, tissue regeneration, and systemic health. Age-related changes manifest as altered blood cell composition, functional decline in hematopoietic stem cells (HSCs), and deterioration of the bone marrow niche. Beyond hematologic dysfunction, hematopoietic aging acts as a systemic amplifier of age-related diseases through clonal hematopoiesis and inflammatory remodeling. This review integrates recent insights into the mechanisms and systemic impacts of hematopoietic aging, reframing it as a modifiable axis of systemic aging. We highlight emerging rejuvenation strategies-senolytics, metabolic reprogramming, and microbiota-targeted therapies-that aim to restore hematopoietic and immune function, offering promising avenues to improve healthspan and reduce age-related multimorbidity.
    Keywords:  aging; healthspan; hematopoiesis; hematopoietic stem cells; inflammation
    DOI:  https://doi.org/10.1111/acel.70385
  2. Rinsho Ketsueki. 2025 ;66(12): 1545-1551
    [Dysfunction and premature aging of hematopoietic stem cells in Down syndrome].
    Mariko Morii.
      
    Keywords:  Down syndrome; Epigenetics; Hematopoietic stem cells; Hmga2
    DOI:  https://doi.org/10.11406/rinketsu.66.1545
  3. Genome Biol. 2026 Jan 16.
    An inflammatory and quiescent HSC subpopulation expands with age in humans.
    Ksenia R Safina, Basit Salik, Dylan Kotliar, Michelle Curtis, Jonathan D Good, Chen Weng, Shawn David, Soumya Raychaudhuri, Antonia Kreso, Jennifer J Trowbridge, Vijay G Sankaran, Peter van Galen.
      Aging of the blood system impacts systemic health and can be traced to hematopoietic stem cells (HSCs). Despite multiple reports on human HSC aging, a unified map detailing their molecular age-related changes is lacking. We developed a consensus map of gene expression in HSCs by integrating seven single-cell datasets. This map reveals previously unappreciated heterogeneity within the HSC population. It also links inflammatory pathway activation (TNF/NFκB, AP-1) and quiescence within a single gene expression program. This program dominates an inflammatory HSC subpopulation that increases with age, highlighting a potential target for further experimental studies and anti-aging interventions.
    DOI:  https://doi.org/10.1186/s13059-026-03936-z
  4. Proc Natl Acad Sci U S A. 2026 Jan 20. 123(3): e2426767123
    CCR5 marks a subset of mouse hematopoietic stem cells that are myeloid primed and expand with age.
    Leyla Yılmaz, Allison Banuelos, Michelle Baez, Uyen Le, Nardin Georgeos, Monika Zukowska, Allison Zhang, Rahul Sinha, Irving L Weissman.
      Hematopoietic stem cells (HSCs) are multipotent self-renewing cells that give rise to all types of blood cells. Past research has identified that long-term hematopoietic stem cells in young mice and humans produce a balanced output of lymphoid and myeloid cells, while in old age, they are largely replaced by myeloid-biased HSCs (My-HSC). It has not yet been determined whether this transition results from epigenetic changes in a single population of HSC or if two or more subsets of HSCs exist that gain or lose dominance with age via processes of selection. Whether epigenetic change or competition, several characteristics of each may exist to ensure that the appropriate subset is placed in niches that support them. HSC can be mobilized into the blood and home selectively to target tissues via expression of "homing receptors," but these molecules do not determine their intraorgan migration to appropriate niches. Chemokines are the class of molecules that determine intraorgan migration of cells. Here, we show that the chemokine receptor CCR5 is mainly expressed on My-HSCs, and therefore, the frequency of CCR5+ HSCs increases with age. Aged HSCs negative for CCR5 expression generate lower frequency of myeloid cells than lymphoid cells upon transplantation into recipients. Additionally, disruption of the CCL5-CCR5 signaling axis changes frequency of lymphoid populations in peripheral blood of aged mice, supporting research that shows the depletion of My-HSCs can result in the rejuvenation of adaptive immunity.
    Keywords:  CCR5; HSC; aging
    DOI:  https://doi.org/10.1073/pnas.2426767123
  5. Biomaterials. 2026 Jan 12. pii: S0142-9612(26)00013-X. [Epub ahead of print]330 123989
    Iron oxide nanoparticles-driven mitochondrial renewal rejuvenates the aged bone marrow niche.
    Xiaoqing Sun, Xingyou Wang, Meihua Zhang, Shuyao Liu, Yue Zhu, Jing He, Yao Wu.
      With the aging population, treating age-related osteoporosis remains challenging due to the dysfunctional bone marrow microenvironment characterized by chronic inflammation, metabolic dysregulation, and impaired mitochondrial function in senescent cells. While mitochondrial transfer from macrophages to bone marrow mesenchymal stem cells (BMSCs) offers a promising therapeutic avenue, its efficacy is limited in aged niches where donor mitochondria exhibit functional deficits and poor recipient compatibility. We engineered KGM-PEG-SPIONs, functionalized Fe3O4 nanoparticles that enhance donor mitochondrial quality via autophagy activation and Fe-S cluster biogenesis, promote M2 macrophage polarization, and improve compatibility with the oxidative and inflammatory environment of senescent BMSCs. These M2-like mitochondria are transferred through connexin 43 gap junctions, restoring membrane potential, ATP production, calcium homeostasis, and osteogenic differentiation in recipient cells. In aged osteoporotic models, KGM-PEG-SPION-functionalized scaffolds remodel immune niches and promote bone formation. By integrating organelle quality control with environment-adapted mitochondrial transfer, this strategy surpasses approaches focusing solely on transfer quantity or polarization, establishing a programmable nanoplatform for organelle-based regeneration.
    Keywords:  Autophagy; Fe–S cluster; Mitochondrial biogenesis; Mitochondrial transfer; Senescent macrophage polarization; Senile osteoporotic
    DOI:  https://doi.org/10.1016/j.biomaterials.2026.123989
  6. J Cell Biol. 2026 Apr 06. pii: e202505110. [Epub ahead of print]225(4):
    Potassium ion homeostasis modulates mitochondrial function.
    Adam James Waite, Beiduo Rao, Elizabeth Schinski, Nathaniel H Thayer, Manuel Hotz, Austin E Y T Lefebvre, Celeste Sandoval, Daniel E Gottschling.
      Age-associated decline in mitochondrial membrane potential (MMP) is a ubiquitous aspect of eukaryotic organisms and is associated with many aging-related diseases. However, it is not clear whether this decline is a cause or consequence of aging, and therefore whether interventions to reduce MMP decline are a viable strategy to promote healthier aging and longer lifespans. We developed a screening platform in Saccharomyces cerevisiae to identify mutations that slowed or abrogated the age-associated decline in MMP. Characterization of the longest-lived mutant revealed that reduced internal potassium increased MMP and extended lifespan. Distinct interventions improved cellular MMP and lifespan: deleting a potassium transporter; altering the balance between kinases and phosphatases that control potassium transporter activity; and reducing available potassium in the environment. Similarly, in isolated mitochondria, reducing the concentration of potassium was sufficient to increase MMP. These data indicate that the most abundant monovalent cation in eukaryotic cells plays a critical role in tuning mitochondrial function, consequently impacting lifespan.
    DOI:  https://doi.org/10.1083/jcb.202505110
  7. Genomics Inform. 2026 Jan 13.
    Mitochondrial transfer in cancer: mechanisms, immune evasion, and therapeutic opportunities.
    Hye In Ka, Hyun Goo Woo.
      Intercellular mitochondrial transfer (MT) is emerging as a transformative communication axis in cancer biology. Intact mitochondria or mitochondrial components can be exchanged between tumor cells, stromal elements, and immune cells via tunneling nanotubes, extracellular vesicles, cell fusion, or phagocytic uptake. This organelle exchange enables metabolic adaptation by restoring OXPHOS (oxidative phosphorylation), increasing ATP production, and enhancing survival in hostile environments. Conversely, tumor cells also hijack mitochondria from cytotoxic lymphocytes thereby undermining immune function and contributing to immune escape and tumor progression. These converging metabolic exchanges fuel immune evasion, metastatic potential, and resistance to chemotherapy, radiation, and immunotherapy. Cutting-edge tracing tools, including mitochondrial reporter proteins and single-cell mitochondrial genome lineage mapping, have uncovered MT events both in vitro and in vivo. Therapeutic strategies designed to block mitochondrial trafficking, inhibit nanotube formation or vesicle uptake, or enhance immune cell mitochondrial resilience hold promise for tumor sensitization and restoration of antitumor immunity. A deeper understanding of MT provides novel insight into cancer metabolism and intercellular communication, offering a foundation for future therapeutic innovation and potential clinical application as both a biomarker and a therapeutic target.
    Keywords:  Cancer; Immune Evasion; Mitochondria; Mitochondrial Transfer
    DOI:  https://doi.org/10.1186/s44342-025-00064-1
  8. Immunol Rev. 2026 Jan;337(1): e70084
    Cellular Senescence, Inflammaging and Cardiovascular Disease.
    Lukas Zanders, Denada Arifaj, Julian U G Wagner, Stefanie Dimmeler.
      Aging is the most important yet unmodifiable risk factor for cardiovascular disease (CVD). As a result, targeting cardiovascular aging has emerged as a promising strategy to promote long-term cardiovascular health. This review summarizes current knowledge on the effects of aging within the cardiovascular system as well as systemic processes that modulate them. We highlight the roles of cellular senescence and the senescence-associated secretory phenotype (SASP), emphasizing their heterogeneous contributions to chronic low-grade inflammation and tissue remodeling-collectively termed inflammaging. Advances in biomarkers, animal models, and systems biology approaches have deepened our understanding of the interplay between senescence, inflammaging, and cardiovascular dysfunction, including the pivotal role of macrophages in senescent cell clearance. Therapeutic strategies are diverse, ranging from senolytic approaches designed to selectively eliminate senescent cells, to SASP modulation, and interventions targeting chronic inflammation and metabolic dysregulation. Of particular interest, drugs already in clinical use-such as metformin and other anti-diabetic agents-show beneficial effects on aging-related pathways, suggesting that their cardiovascular protection may in part reflect anti-aging properties. Despite these advances, therapies directly targeting senescence and inflammaging to reduce the global burden of CVD remain an urgent unmet need.
    Keywords:  cardiovascular disease; cellular senescence; heart failure; inflammaging; senolytic; senomorphic
    DOI:  https://doi.org/10.1111/imr.70084
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