bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2024–01–07
eight papers selected by
Ayesh Seneviratne, Western University



  1. Nat Aging. 2024 Jan 04.
      The decline in stem cell function during aging may affect the regenerative capacity of mammalian organisms; however, the gene regulatory mechanism underlying this decline remains unclear. Here we show that the aging of neural stem and progenitor cells (NSPCs) in the male mouse brain is characterized by a decrease in the generation efficacy of proliferative NSPCs rather than the changes in lineage specificity of NSPCs. We reveal that the downregulation of age-dependent genes in NSPCs drives cell aging by decreasing the population of actively proliferating NSPCs while increasing the expression of quiescence markers. We found that epigenetic deregulation of the MLL complex at promoters leads to transcriptional inactivation of age-dependent genes, highlighting the importance of the dynamic interaction between histone modifiers and gene regulatory elements in regulating transcriptional program of aging cells. Our study sheds light on the key intrinsic mechanisms driving stem cell aging through epigenetic regulators and identifies potential rejuvenation targets that could restore the function of aging stem cells.
    DOI:  https://doi.org/10.1038/s43587-023-00549-0
  2. Nature. 2024 Jan;625(7993): 24-25
      
    Keywords:  Ageing; Genetics; Lab life
    DOI:  https://doi.org/10.1038/d41586-023-04089-w
  3. Br J Sports Med. 2024 Jan 04. pii: bjsports-2023-107683. [Epub ahead of print]
      
    Keywords:  Aging; Frailty
    DOI:  https://doi.org/10.1136/bjsports-2023-107683
  4. Cell Metab. 2023 Dec 22. pii: S1550-4131(23)00458-8. [Epub ahead of print]
      Here, we summarize the current knowledge on eight promising drugs and natural compounds that have been tested in the clinic: metformin, NAD+ precursors, glucagon-like peptide-1 receptor agonists, TORC1 inhibitors, spermidine, senolytics, probiotics, and anti-inflammatories. Multiple clinical trials have commenced to evaluate the efficacy of such agents against age-associated diseases including diabetes, cardiovascular disease, cancer, and neurodegenerative diseases. There are reasonable expectations that drugs able to decelerate or reverse aging processes will also exert broad disease-preventing or -attenuating effects. Hence, the outcome of past, ongoing, and future disease-specific trials may pave the way to the development of new anti-aging medicines. Drugs approved for specific disease indications may subsequently be repurposed for the treatment of organism-wide aging consequences.
    Keywords:  age-related disease; autophagy; metformin; nicotinamide mononucleotide/NAD(+)/sirtuins; senescence
    DOI:  https://doi.org/10.1016/j.cmet.2023.12.007
  5. Geroscience. 2024 Jan 05.
      Wild-type murine models for aging research have lifespans of several years, which results in long experimental duration and late output. Here we explore the short-lived non-inbred Titan mouse (DU6) as a mouse model to test longevity interventions. We show that Titan mice exhibit increased frailty and senescence-associated beta-galactosidase activity at an early age. Dietary intervention attenuates the frailty progression of Titan mice. Additionally, cyclic administration of the senolytic drug Navitoclax at an early age increases the lifespan and reduces senescence-associated beta-galactosidase activity. Our data suggests that Titan mice can serve as a cost-effective and timely model for longevity interventions in mammals.
    Keywords:  Aging; Dietary intervention; Frailty index; Mouse models; Navitoclax
    DOI:  https://doi.org/10.1007/s11357-023-01045-4