bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2025–08–24
five papers selected by
Ayesh Seneviratne, McMaster University
  1. Metallothionein 1 mediates growth and survival of Dnmt3a;Npm1-mutant acute myeloid leukemia.
  2. The emerging role of cellular senescence in amyotrophic lateral sclerosis.
  3. Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.
  4. COVID-19 and vascular ageing: an accelerated yet partially reversible clock?
  5. A change is needed in the landscape of preclinical models to test drugs that target aging.
  1. Haematologica. 2025 Aug 14.
    Metallothionein 1 mediates growth and survival of Dnmt3a;Npm1-mutant acute myeloid leukemia.
    Patricia A Colom Díaz, Jayna J Mistry, Kira A Young, Chih-Hsing Chou, Nathan Boyer, Ross L Levine, Nathan Salomonis, H Leighton Grimes, Jennifer J Trowbridge.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2025.287662
  2. Front Neurosci. 2025 ;19 1599492
    The emerging role of cellular senescence in amyotrophic lateral sclerosis.
    Xingli Tan, Naiyong Gao.
      Cellular senescence is a state of permanent cell cycle arrest and is considered a key contributor to aging and age-related diseases, including amyotrophic lateral sclerosis (ALS). The physiological processes of aging lead to a variety of molecular and cellular phenotypes, and evidence of overlap between ALS and aging-related biomarkers suggests that cell type-specific senescence may be a critical factor in ALS. Senescent microglial cells, astrocytes, and neurons have been detected in ALS patients and animal models. However, while accumulating evidence suggests a potential link between cellular senescence and ALS, this connection remains not yet conclusively established. Importantly, how senescent cells may contribute to the neuropathophysiology of ALS remains largely unknown. Additionally, the growing popularity of anti-aging therapies has highlighted the potential of senescent cell clearance as a promising strategy for treating age-related diseases, including ALS. This review provides an overview of cellular senescence, discusses recent advances in understanding how senescence in different cell types influences ALS pathogenesis, and explores the potential role of anti-senescence therapies in ALS treatment.
    Keywords:  aging; aging of motor neurons; amyotrophic lateral sclerosis; anti-senescence; cellular senescence
    DOI:  https://doi.org/10.3389/fnins.2025.1599492
  3. Nat Aging. 2025 Aug 19.
    Targeting iron-associated protein Ftl1 in the brain of old mice improves age-related cognitive impairment.
    Laura Remesal, Juliana Sucharov-Costa, Yuting Wu, Karishma J B Pratt, Gregor Bieri, Amber Philp, Mason Phan, Turan Aghayev, Charles W White, Elizabeth G Wheatley, Bende Zou, Brandon R Desousa, Julien Couthouis, Isha H Jian, Xinmin S Xie, Yi Lu, Jason C Maynard, Alma L Burlingame, Saul A Villeda.
      Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we identify ferritin light chain 1 (FTL1), an iron-associated protein, as a pro-aging neuronal factor that impairs cognition. Using transcriptomic and mass spectrometry approaches, we detect an increase in neuronal FTL1 in the hippocampus of aged mice, the levels of which correlate with cognitive decline. Mimicking an age-related increase in neuronal FTL1 in young mice alters labile iron oxidation states and promotes synaptic and cognitive features of hippocampal aging. Targeting neuronal FTL1 in the hippocampi of aged mice improves synaptic-related molecular changes and cognitive impairments. Using neuronal nuclei RNA sequencing, we detect changes in metabolic processes, such as ATP synthesis, and boosting these metabolic functions through NADH supplementation mitigated pro-aging effects of neuronal FTL1 on cognition. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.
    DOI:  https://doi.org/10.1038/s43587-025-00940-z
  4. Eur Heart J. 2025 Aug 17. pii: ehaf590. [Epub ahead of print]
    COVID-19 and vascular ageing: an accelerated yet partially reversible clock?
    Syed Bukhari, Marie D Gerhard-Herman, Behnood Bikdeli.
      
    DOI:  https://doi.org/10.1093/eurheartj/ehaf590
  5. Aging Pathobiol Ther. 2024 Dec;6(4): 152-153
    A change is needed in the landscape of preclinical models to test drugs that target aging.
    Warren Ladiges.
      Efficient and reproducible preclinical models for testing drugs or drug combinations that target aging are vital to develop a pipeline that results in a predictable outcome for geroscience research and geriatric medicine. Lifespan as a readout test in laboratory mice has been successful in identifying several drugs that robustly enhance healthy aging, and has provided impactful information for moving to clinical studies. However, it is a costly and time consuming process (about three years), and poorly designed to test drug combinations. Therefore, a more efficient pipeline is needed that would provide an increased number of drugs or drug combinations with promising and predictable outcomes for first in human studies in a shorter time frame. This editorial discusses an alternate system involving prescreening in an invertebrate model (the domestic house cricket) followed by short term cross sectional testing in aging mice. The time frame is about six months, and the system is simple enough to allow testing of multiple drugs concurrently. The cricket to mouse pipeline provides a logical and preclinical translational approach to identify drugs that have the potential to enhance human health at later ages of life.
    Keywords:  Aging intervention; aging mice; drugs and drug combinations; house crickets; preclinical animal models; translational drug testing
    DOI:  https://doi.org/10.31491/apt.2024.12.162
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