bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2025–07–27
six papers selected by
Ayesh Seneviratne, McMaster University
  1. Clonal hematopoiesis in myeloid malignancies and solid tumors.
  2. Non-canonical functions of DNMT3A in hematopoietic stem cells regulate telomerase activity and genome integrity.
  3. PAI-1 is a common driver of aging and diverse diseases.
  4. Sex at birth is not always random - mum's age and genetics can play a part.
  5. How the same brain cells can represent both the perception and memory of faces.
  6. Daily briefing: Rejuvenating the immune system could slow ageing.
  1. Nat Cancer. 2025 Jul 18.
    Clonal hematopoiesis in myeloid malignancies and solid tumors.
    Xiurong Cai, Robert L Bowman, Jennifer J Trowbridge.
      Clonal hematopoiesis (CH) results from clonal expansion of hematopoietic stem cells. In specific contexts, CH is linked with an increased risk of blood cancers and mortality in individuals with solid tumors. To understand the mechanisms and clinical relevance of this association, it is crucial to explore the reciprocal relationship between CH and cancer. Here, we provide an updated summary of the mechanisms known to drive CH in blood cancers and solid tumors. In addition, we review proposed strategies to intercept CH and examine their impact on solid tumor-directed therapies, including immunostimulatory therapies.
    DOI:  https://doi.org/10.1038/s43018-025-01014-0
  2. Cell Stem Cell. 2025 Jul 10. pii: S1934-5909(25)00256-5. [Epub ahead of print]
    Non-canonical functions of DNMT3A in hematopoietic stem cells regulate telomerase activity and genome integrity.
    Infencia Xavier Raj, Won Kyun Koh, Jessica Harrison, Christine R Zhang, Barbara Soares, Roberta Amato, Aishwarya Krishnan, David R O'Leary, Hassan Bjeije, Tyler M Parsons, Wentao Han, Andrew L Young, Ting Wang, Luis F Z Batista, Grant A Challen.
      DNMT3A is a critical regulator of hematopoietic stem cell (HSC) fate decisions and the most recurrently mutated gene in human clonal hematopoiesis (CH). DNMT3A is described as a DNA methyltransferase enzyme, but cells with DNMT3A loss of function show minor changes in DNA methylation that do not correlate with altered gene expression. To explore the possibility that Dnmt3a has DNA-methylation-independent functions in HSCs, we created an allelic series of mice with varying levels of DNA-methylation-impaired Dnmt3a. Clonal expansion of Dnmt3a-deficient HSCs was rescued by Dnmt3a proteins lacking DNA methylation capacity, suggesting that Dnmt3a has important non-canonical functions in HSCs. Dnmt3a-null HSCs can be transplanted indefinitely, implying the ability to circumvent mechanisms that limit the replicative lifespan of HSCs, such as telomere shortening. Dnmt3a-null HSCs show increased telomerase activity and sustain telomere length over serial transplantation, revealing a previously unidentified role for DNMT3A mutations in regulating HSC longevity that is unrelated to DNA methylation function.
    Keywords:  DNA methylation; DNMT3A; hematopoietic stem cell; telomerase; telomere
    DOI:  https://doi.org/10.1016/j.stem.2025.06.010
  3. Biomed J. 2025 Jul 18. pii: S2319-4170(25)00066-6. [Epub ahead of print] 100892
    PAI-1 is a common driver of aging and diverse diseases.
    Alireza Khoddam, Toshio Miyata, Douglas Vaughan.
      Plasminogen activator inhibitor-1 (PAI-1) is a key driver of aging and contributes to diverse pathologies. This review examines PAI-1's multifaceted contributions to aging. At the cellular level, PAI-1 amplifies senescence, exhausts stem cell niches, and disrupts metabolism. These cellular alterations translate into physiological decline: PAI-1 drives cardiovascular aging by promoting vascular senescence and arterial stiffening, contributes to cognitive decline by impairing amyloid-beta clearance, fuels cancer progression through angiogenesis and immune suppression, and exacerbates muscle atrophy by hindering regeneration. A rare loss-of-function SERPINE1 mutation extends lifespan, illustrating how lifelong PAI-1 reduction can positively impact the human healthspan. Looking forward, targeting PAI-1 with inhibitors could mitigate senescence, restore stem cell function, improve metabolic profile, enhance physiological health, and promise a longer healthspan.
    Keywords:  Aging; Cognitive Decline; Muscle Atrophy; PAI-1; Senescence
    DOI:  https://doi.org/10.1016/j.bj.2025.100892
  4. Nature. 2025 Jul 18.
    Sex at birth is not always random - mum's age and genetics can play a part.
    Rachel Fieldhouse.
      
    Keywords:  Ageing; Genetics
    DOI:  https://doi.org/10.1038/d41586-025-02244-z
  5. Nature. 2024 May 22.
    How the same brain cells can represent both the perception and memory of faces.
      
    Keywords:  Brain; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-024-01511-9
  6. Nature. 2024 May 08.
    Daily briefing: Rejuvenating the immune system could slow ageing.
    Flora Graham.
      
    DOI:  https://doi.org/10.1038/d41586-024-01391-z
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