bims-cesemi Biomed News
on Cellular senescence and mitochondria
Issue of 2026–02–01
thirteen papers selected by
Julio Cesar Cardenas, Universidad Mayor
  1. Mitochondrial protein carboxyl-terminal alanine-threonine tailing promotes human glioblastoma growth by regulating mitochondrial function.
  2. Organelles stick together through PDZD8-mediated condensate formation.
  3. Mitochondria transfer from myocytes to endothelial cells Promotes angiogenesis in skeletal muscle.
  4. Metabolic approach to counteract skin aging.
  5. Muscle stem cells trade functionality for survival.
  6. The surprisingly big health benefits of just a little exercise.
  7. OGDHL promotes prostate cancer progression and regulates neuroendocrine marker expression and nucleotide abundance.
  8. Inhibition of TRPC3-Nox2 Complex Formation Ameliorates Skeletal Muscle Atrophy.
  9. Deciphering the causal nexus of mitochondrial biology with breast cancer.
  10. Longevity is in the genes: half of lifespan is heritable.
  11. Role of lysosomal morphology in aging and age-related diseases.
  12. Heritability of intrinsic human life span is about 50% when confounding factors are addressed.
  13. Myo-Inositol modulates AKT signalling, mitochondrial protein expression and intracellular Ca²⁺dynamics in human dermal fibroblasts.
  1. Elife. 2026 Jan 29. pii: RP99438. [Epub ahead of print]13
    Mitochondrial protein carboxyl-terminal alanine-threonine tailing promotes human glioblastoma growth by regulating mitochondrial function.
    Bei Zhang, Ting Cai, Esha Reddy, Yuanna Wu, Isha Mondal, Yinglu Tang, Adaeze Scholastical Gbufor, Jerry Wang, Yawei Shen, Qing Liu, Raymond Sun, Winson S Ho, Rongze Olivia Lu, Zhihao Wu.
      The rapid and sustained proliferation of cancer cells necessitates increased protein production, which, along with their disrupted metabolism, elevates the likelihood of translation errors. Ribosome-associated quality control (RQC), a recently identified mechanism, mitigates ribosome collisions resulting from frequent translation stalls. However, the precise pathophysiological role of the RQC pathway in oncogenesis remains ambiguous. Our research centered on the pathogenic implications of mitochondrial stress-induced protein carboxyl-terminal alanine and threonine tailing (msiCAT-tailing), a specific RQC response to translational arrest on the outer mitochondrial membrane, in human glioblastoma multiforme (GBM). The presence of msiCAT-tailed mitochondrial proteins was observed commonly in glioblastoma stem cells (GSCs). The exogenous introduction of the mitochondrial ATP synthase F1 subunit alpha (ATP5α) protein, accompanied by artificial CAT-tail mimicking sequences, enhanced mitochondrial membrane potential (ΔΨm) and inhibited the formation of the mitochondrial permeability transition pore (MPTP). These alterations in mitochondrial characteristics provided resistance to staurosporine (STS)-induced apoptosis in GBM cells. Consequently, msiCAT-tailing can foster cell survival and migration, whereas blocking msiCAT-tailing via genetic or pharmacological intervention can impede GBM cell overgrowth.
    Keywords:  cancer biology; carboxyl-terminal alanine and threonine tailing; cell biology; glioblastoma; human; mitochondria; ribosome-associated quality control
    DOI:  https://doi.org/10.7554/eLife.99438
  2. Nat Rev Mol Cell Biol. 2026 Jan 29.
    Organelles stick together through PDZD8-mediated condensate formation.
    Lisa Heinke.
      
    DOI:  https://doi.org/10.1038/s41580-026-00950-8
  3. Mitochondrion. 2026 Jan 24. pii: S1567-7249(26)00006-1. [Epub ahead of print] 102116
    Mitochondria transfer from myocytes to endothelial cells Promotes angiogenesis in skeletal muscle.
    Yu-Feng Long, Ai-Jun Huang, Shuo Tang, Zhen Xu, Ming-Yue Wu, Kai Liu, Ze-Cai Chen, Lei Qin, Bing-Yang Dai, Cheng Dong, Wing-Hoi Cheung, Xin-Luan Wang, Da-Zhi Yang.
      Skeletal muscle and vascular health are closely interconnected, yet the mechanisms underlying their crosstalk remain poorly understood. This study investigates the role of mitochondria transfer from myocytes to endothelial cells. Using in vitro 2D and 3D coculture systems, combined with protein-level and functional analyses, we show that mitochondria are transferred via extracellular vesicles in a Rab7-dependent and cellular connection-independent manner. Connexin 43 (CX43) inhibition downregulating Growth-Associated Protein 43 (GAP43) but enhances mitochondria transfer, accompanied by increasing Rab7. Transferred mitochondria promote endothelial cells proliferation, migration, ATP production, and angiogenesis, which could be the key processes in preserving vascular integrity and muscle function. Our study indicated that the aging-associated decline in CX43 and mitochondrial quality exacerbates muscle atrophy by facilitating the transfer of dysfunctional mitochondria. These findings uncover a novel mechanism of muscle-vessel communication and highlight mitochondria transfer as a potential therapeutic target for aging-related muscular and vascular deterioration. New and Noteworthy. Mitochondria transfer is a way for cell communication. However, mitochondria transfer between myocyte and endothelial cell remains unknown. Here, we demonstrates that mitochondria transfer occurs between myocytes and endothelial cells. Interestingly, inhibition of CX43 leads to a decrease in GAP43 expression, while simultaneously upregulating Rab7 and enhancing mitochondria transfer from myocytes to endothelial cells. Furthermore, we reveal that Rab7-induced mechanism mediates the transfer of both functional and impaired mitochondria from myocytes to endothelial cells.
    Keywords:  Endothelial cells; Mitochondria transfer; Muscle; Myocytes; Vessel
    DOI:  https://doi.org/10.1016/j.mito.2026.102116
  4. Br J Dermatol. 2026 Jan 29. pii: ljag026. [Epub ahead of print]
    Metabolic approach to counteract skin aging.
    Mauro Picardo, Qinyi Chen.
      
    DOI:  https://doi.org/10.1093/bjd/ljag026
  5. Science. 2026 Jan 29. 391(6784): 444
    Muscle stem cells trade functionality for survival.
    Julia von Maltzahn.
      During aging, stem cell persistence is favored over functionality, resulting in delayed responses to injury.
    DOI:  https://doi.org/10.1126/science.aed3298
  6. Nature. 2026 Jan;649(8099): 1092-1094
    The surprisingly big health benefits of just a little exercise.
    Mariana Lenharo.
      
    Keywords:  Epidemiology; Public health
    DOI:  https://doi.org/10.1038/d41586-026-00237-0
  7. Mol Cancer Res. 2026 Jan 27.
    OGDHL promotes prostate cancer progression and regulates neuroendocrine marker expression and nucleotide abundance.
    Matthew J Bernard, Andrea Gallardo, Angel Ruiz, Johnny A Diaz, Nicholas M Nunley, Rachel N Dove, Shile Zhang, Ernie Lee, Kylie Y Heering, Grigor Varuzhanyan, Sachi Bopardikar, Takao Hashimoto, Raag Agrawal, Chad M Smith, Blake R Wilde, Nedas Matulionis, Helen M Richards, Sandy Che-Eun S Lee, Marina N Sharifi, Joshua M Lang, Shuang G Zhao, Owen N Witte, Michael C Haffner, David B Shackelford, Paul C Boutros, Heather R Christofk, Andrew S Goldstein.
      As cancer cells evade therapeutic pressure and adopt alternate lineage identities not commonly observed in the tissue of origin, they likely adopt alternate metabolic programs to support their evolving demands. Targeting these alternative metabolic programs in distinct molecular subtypes of aggressive prostate cancer may lead to new therapeutic approaches to combat treatment-resistance. We identify the poorly studied metabolic enzyme Oxoglutarate Dehydrogenase-Like (OGDHL), named for its structural similarity to the tricarboxylic acid (TCA) cycle enzyme Oxoglutarate Dehydrogenase (OGDH), as an unexpected regulator of tumor growth, treatment-induced lineage plasticity, and DNA Damage in prostate cancer. While OGDHL has been described as a tumor-suppressor in various cancers, we find that its loss impairs prostate cancer cell proliferation and tumor formation. Loss of OGDHL reduces nucleotide synthesis, induces accumulation of the DNA damage response marker ƔH2AX, and alters Androgen Receptor inhibition-induced plasticity. Our data suggest that OGDHL has minimal impact on TCA cycle activity, and that mitochondrial localization is not required for its regulation of nucleotide metabolism. Finally, we demonstrate that OGDHL expression is tightly correlated with neuroendocrine differentiation in clinical prostate cancer, and that knockdown of OGDHL impairs growth of cell line models of neuroendocrine prostate cancer. These findings underscore the importance of investigating poorly characterized metabolic genes as potential regulators of distinct molecular subtypes of aggressive cancer. Implications: OGDHL emerged as an unexpected metabolic dependency associated with lineage plasticity and neuroendocrine differentiation, implicating poorly studied metabolic enzymes as potential targets for treatment-resistant prostate cancer.
    DOI:  https://doi.org/10.1158/1541-7786.MCR-25-0913
  8. Antioxidants (Basel). 2025 Dec 26. pii: 38. [Epub ahead of print]15(1):
    Inhibition of TRPC3-Nox2 Complex Formation Ameliorates Skeletal Muscle Atrophy.
    Yuri Kato, Di Wu, Tomoya Ito, Yara Atef, Koichi Ayukawa, Xinya Mi, Kazuhiro Nishiyama, Akiyuki Nishimura, Motohiro Nishida.
      Skeletal muscle atrophy underlies sarcopenia, frailty, and muscular dystrophies, but the molecular mechanisms linking oxidative stress to muscle degeneration remain incompletely understood. We previously identified protein complex formation between transient receptor potential canonical 3 (TRPC3) and NADPH oxidase 2 (Nox2) as a key driver of anthracycline-induced myocardial atrophy. Here, we investigated whether this complex also contributes to skeletal muscle wasting. In skeletal muscle from sciatic nerve transection model mice and Duchenne muscular dystrophy (mdx) mice, TRPC3-Nox2 complex formation was enhanced. TRPC3 deletion significantly attenuated denervation-induced soleus atrophy and reduced reactive oxygen species (ROS) production. TRPC3-Nox2 complex formation was upregulated in the soleus muscle (SM) of mdx mice. Pharmacological disruption of the TRPC3-Nox2 interaction improved muscle size and strength and reduced plasma creatine kinase in mdx mice. A recombinant adeno-associated virus (AAV) encoding a TRPC3 C-terminal peptide was used to suppress TRPC3-Nox2 complex formation in vivo. AAV-mediated expression of TRPC3 C-terminal peptide mitigated muscle wasting (CSA) in mdx mice, while muscle strength and plasma CK were not significantly improved. Thus, TRPC3-Nox2 complex formation may be a pivotal driver of oxidative stress-mediated skeletal muscle atrophy. Targeting this protein-protein interaction represents a promising therapeutic strategy for Duchenne muscular dystrophy (DMD) and other intractable muscle-wasting disorders.
    Keywords:  Nox2; TRPC3; protein–protein interaction; skeletal muscle atrophy
    DOI:  https://doi.org/10.3390/antiox15010038
  9. Discov Oncol. 2026 Jan 26.
    Deciphering the causal nexus of mitochondrial biology with breast cancer.
    Dongsong Liu, Hongfang Xu, Yan Yan, Bingnan Wang, Wangjun Yan.
      
    Keywords:  Breast cancer; Genetic causality; Mendelian randomization; Mitochondrial biology
    DOI:  https://doi.org/10.1007/s12672-026-04500-8
  10. Nature. 2026 Jan 29.
    Longevity is in the genes: half of lifespan is heritable.
    Max Kozlov.
      
    DOI:  https://doi.org/10.1038/d41586-026-00300-w
  11. Ageing Res Rev. 2026 Jan 23. pii: S1568-1637(26)00025-5. [Epub ahead of print]115 103033
    Role of lysosomal morphology in aging and age-related diseases.
    Huimin Liu, Haiqing Tang, Shanshan Pang.
      Lysosomes are responsible for clearing cellular waste and facilitating material recycling, thus playing a crucial role in maintaining cellular homeostasis and even in resisting the development of various diseases. Lysosomes are highly dynamic organelles. While typically exhibiting a vesicular morphology, lysosomes can remodel into tubular structures under specific conditions; this morphological plasticity underpins their functional complexity. Aging triggers significant lysosomal morphological remodeling and functional decline, contributing to the development of age-related diseases, notably neurodegenerative disorders. Although lysosomal function has been extensively studied in age-related diseases, the mechanisms driving aging-associated morphological alterations and their pathophysiological significance remain elusive. This review synthesizes current knowledge on the regulation of lysosomal morphology and its changes and functions during aging and in age-related diseases. We propose that altered lysosomal morphology represents not merely a hallmark of aging, but also a significant determinant of lysosomal and cellular functions during aging. Targeting lysosomal morphology holds promise as an emerging strategy for counteracting functional deterioration in aged lysosomes and mitigating associated disease pathogenesis.
    Keywords:  Aging; Lysosomes; Morphology; Tubulation; Vesicular enlargement
    DOI:  https://doi.org/10.1016/j.arr.2026.103033
  12. Science. 2026 Jan 29. 391(6784): 504-510
    Heritability of intrinsic human life span is about 50% when confounding factors are addressed.
    Ben Shenhar, Glen Pridham, Thaís Lopes De Oliveira, Naveh Raz, Yifan Yang, Joris Deelen, Sara Hägg, Uri Alon.
      How heritable is human life span? If genetic heritability is high, longevity genes can reveal aging mechanisms and inform medicine and public health. However, current estimates of heritability are low-twin studies show heritability of only 20 to 25%, and recent large pedigree studies suggest it is as low as 6%. Here we show that these estimates are confounded by extrinsic mortality-deaths caused by extrinsic factors such as accidents or infections. We use mathematical modeling and analyses of twin cohorts raised together and apart to correct for this factor, revealing that heritability of human life span due to intrinsic mortality is above 50%. Such high heritability is similar to that of most other complex human traits and to life-span heritability in other species.
    DOI:  https://doi.org/10.1126/science.adz1187
  13. Sci Rep. 2026 Jan 28.
    Myo-Inositol modulates AKT signalling, mitochondrial protein expression and intracellular Ca²⁺dynamics in human dermal fibroblasts.
    Paola Zanfardino, Alessandro Amati, Domenico Iacobellis, Matilde Colella, Vittoria Petruzzella.
      
    Keywords:  AKT; Calcium; Mitochondria; Myoinositol; Oxidative phosphorylation; Phosphoinositides
    DOI:  https://doi.org/10.1038/s41598-026-37423-z
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