bims-cesemi Biomed News
on Cellular senescence and mitochondria
Issue of 2025–02–09
four papers selected by
Julio Cesar Cardenas, Universidad Mayor
  1. Bifidobacterium adolescentis-derived nicotinic acid improves host skeletal muscle mitochondrial function to ameliorate sarcopenia.
  2. Author Correction: Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog.
  3. A BCL-xL/BCL-2 PROTAC effectively clears senescent cells in the liver and reduces MASH-driven hepatocellular carcinoma in mice.
  4. Omega-3 supplements slow biological ageing.
  1. Cell Rep. 2025 Feb 04. pii: S2211-1247(25)00036-1. [Epub ahead of print]44(2): 115265
    Bifidobacterium adolescentis-derived nicotinic acid improves host skeletal muscle mitochondrial function to ameliorate sarcopenia.
    Zeng Zhang, Quan Guo, Zhihan Yang, Yukai Sun, Shuaiming Jiang, Yangli He, Jiahe Li, Jiachao Zhang.
      Sarcopenia significantly diminishes quality of life and increases mortality risk in older adults. While the connection between the gut microbiome and muscle health is recognized, the underlying mechanisms are poorly understood. In this study, shotgun metagenomics revealed that Bifidobacterium adolescentis is notably depleted in individuals with sarcopenia, correlating with reduced muscle mass and function. This finding was validated in aged mice. Metabolomics analysis identified nicotinic acid as a key metabolite produced by B. adolescentis, linked to improvements in muscle mass and functionality in individuals with sarcopenia. Mechanistically, nicotinic acid restores nicotinamide adenine dinucleotide (NAD+) levels in muscle, inhibits the FoxO3/Atrogin-1/Murf-1 axis, and promotes satellite cell proliferation, reducing muscle atrophy. Additionally, NAD+ activation enhances the silent-information-regulator 1 (SIRT1)/peroxisome-proliferator-activated-receptor-γ-coactivator 1-alpha (PGC-1α) axis, stimulating mitochondrial biogenesis and promoting oxidative metabolism in slow-twitch fibers, ultimately improving muscle function. Our findings suggest that B. adolescentis-derived nicotinic acid could be a promising therapeutic strategy for individuals with sarcopenia.
    Keywords:  Bifidobacterium adolescentis; CP: Metabolism; CP: Microbiology; NAD+; gut microbiome; mitochondria biogenesis; multi-omics; nicotinic acid; sarcopenia; skeletal muscle
    DOI:  https://doi.org/10.1016/j.celrep.2025.115265
  2. Nat Aging. 2025 Jan 31.
    Author Correction: Generation of a selective senolytic platform using a micelle-encapsulated Sudan Black B conjugated analog.
    Sophia Magkouta, Dimitris Veroutis, Angelos Papaspyropoulos, Maria Georgiou, Nikolaos Lougiakis, Natassa Pippa, Sophia Havaki, Anastasia Palaiologou, Dimitris-Foivos Thanos, Konstantinos Kambas, Nefeli Lagopati, Nikos Boukos, Nicole Pouli, Panagiotis Marakos, Athanassios Kotsinas, Dimitris Thanos, Konstantinos Evangelou, Fotios Sampaziotis, Constantin Tamvakopoulos, Stergios Pispas, Russell Petty, Nicholas Kotopoulos, Vassilis G Gorgoulis.
      
    DOI:  https://doi.org/10.1038/s43587-025-00820-6
  3. Nat Aging. 2025 Jan 31.
    A BCL-xL/BCL-2 PROTAC effectively clears senescent cells in the liver and reduces MASH-driven hepatocellular carcinoma in mice.
    Yang Yang, Natacha Jn-Simon, Yonghan He, Chunbao Sun, Peiyi Zhang, Wanyi Hu, Tian Tian, Huadong Zeng, Sreenivasulu Basha, Araceli S Huerta, Lu-Zhe Sun, Xian-Ming Yin, Robert Hromas, Guangrong Zheng, Liya Pi, Daohong Zhou.
      Accumulation of senescent cells (SnCs) plays a causative role in many age-related diseases and has also been implicated in the pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Senolytics that can selectively kill SnCs have the potential to be developed as therapeutics for these diseases. Here we report the finding that 753b, a dual BCL-xL/BCL-2 proteolysis-targeting chimera (PROTAC), acts as a potent and liver-tropic senolytic. We found that treatment with 753b selectively reduced SnCs in the liver in aged mice and STAM mice in part due to its sequestration in the liver. Moreover, 753b treatment could effectively reduce the progression of MASLD and the development of hepatocellular carcinoma (HCC) in STAM mice even after the mice developed substantial metabolic dysfunction-associated steatohepatitis (MASH) and hepatic fibrosis. These findings suggest that BCL-xL/BCL-2 PROTACs have the potential to be developed as therapeutics for MASLD to reduce MASH-driven HCC.
    DOI:  https://doi.org/10.1038/s43587-025-00811-7
  4. Nature. 2025 Feb 03.
    Omega-3 supplements slow biological ageing.
    Felicity Nelson.
      
    Keywords:  Ageing; Epigenetics; Molecular biology
    DOI:  https://doi.org/10.1038/d41586-025-00355-1
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