bims-agimec Biomed News
on Aging mechanisms
Issue of 2025–01–12
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. Dog Aging: A Comprehensive Review of Molecular, Cellular, and Physiological Processes.
  2. Functional Diversity of Senescent Cells in Driving Aging Phenotypes and Facilitating Tissue Regeneration.
  3. From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications.
  4. Brain aging and rejuvenation at single-cell resolution.
  5. Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.
  6. Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions.
  7. Targeting Mitochondria in Glioma: New Hopes for a Cure.
  1. Cells. 2024 Dec 18. pii: 2101. [Epub ahead of print]13(24):
    Dog Aging: A Comprehensive Review of Molecular, Cellular, and Physiological Processes.
    Gabriella Guelfi, Camilla Capaccia, Martina Tedeschi, Antonello Bufalari, Leonardo Leonardi, Beniamino Cenci-Goga, Margherita Maranesi.
      The aging process is a multifactorial biological phenomenon starting at birth and persisting throughout life, characterized by a decline in physiological functions and adaptability. This decline results in the diminished capacity of aging organisms to respond to environmental changes and stressors, leading to reduced efficiency in metabolic, immune, and hormonal functions. As behavioral flexibility wanes, older individuals face longer recovery times and increased vulnerability to diseases. While early research proposed nine core hallmarks of mammalian aging, recent studies have expanded this framework to twelve key characteristics: epigenetic changes, genomic instability, telomere shortening, loss of proteostasis, altered metabolism, mitochondrial dysfunction, cellular senescence, disrupted intercellular communication, stem cell depletion, immune system dysfunction, accumulation of toxic metabolites, and dysbiosis. Given the growing interest in the aging area, we propose to add a new hallmark: impaired water homeostasis. This potential hallmark could play a critical role in aging processes and might open new directions for future research in the field. This review enhances our understanding of the physiological aspects of aging in dogs, suggesting new clinical intervention strategies to prevent and control issues that may arise from the pathological degeneration of these hallmarks.
    Keywords:  aging dog; aging hallmarks; epigenetic changes; physiological decline
    DOI:  https://doi.org/10.3390/cells13242101
  2. J Biochem. 2025 Jan 06. pii: mvae098. [Epub ahead of print]
    Functional Diversity of Senescent Cells in Driving Aging Phenotypes and Facilitating Tissue Regeneration.
    Yasuhiro Nakano, Yoshikazu Johmura.
      As the global population continues to age, understanding the complex role of cellular senescence and its implications in healthy lifespans has gained increasing prominence. Cellular senescence is defined as the irreversible cessation of cell proliferation, accompanied by the secretion of a range of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP), in response to various cellular stresses. While the accumulation of senescent cells has been strongly implicated in the aging process and the pathogenesis of age-related diseases owing to their pro-inflammatory properties, recent research has also highlighted their essential roles in processes such as tumour suppression, tissue development, and repair. This review provides a comprehensive examination of the dual nature of senescent cells, evaluating their deleterious contributions to chronic inflammation, tissue dysfunction, and disease, as well as their beneficial roles in maintaining physiological homeostasis. Additionally, we explored the therapeutic potential of senolytic agents designed to selectively eliminate detrimental senescent cells while considering the delicate balance between transient and beneficial senescence and the persistence of pathological senescence. A deeper understanding of these dynamics is critical to develop novel interventions aimed at mitigating age-related dysfunctions and enhancing healthy life expectancies.
    Keywords:  Age-related diseases; Cellular senescence; Healthspan; Senolytics; Tissue regeneration
    DOI:  https://doi.org/10.1093/jb/mvae098
  3. Cells. 2024 Dec 12. pii: 2052. [Epub ahead of print]13(24):
    From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications.
    Timur Saliev, Prim B Singh.
      Cellular rejuvenation therapies represent a transformative frontier in addressing age-related decline and extending human health span. By targeting fundamental hallmarks of aging-such as genomic instability, epigenetic alterations, mitochondrial dysfunction, and cellular senescence-these therapies aim to restore youthful functionality to cells and tissues, offering new hope for treating degenerative diseases. Recent advancements have showcased a range of strategies, including epigenetic reprogramming, senolytic interventions, mitochondrial restoration, stem cell-based approaches, and gene-editing technologies like CRISPR. Each modality has demonstrated substantial potential in preclinical models and is now being cautiously explored in early-stage clinical trials. However, translating these therapies from the laboratory to clinical practice presents unique challenges: safety concerns, delivery precision, complex regulatory requirements, ethical considerations, and high costs impede widespread adoption. This review examines the current landscape of cellular rejuvenation, highlighting key advancements, potential risks, and the strategies needed to overcome these hurdles.
    Keywords:  CRISPR; induced pluripotent stem cells; mesenchymal stem cells; rejuvenation; senolytics
    DOI:  https://doi.org/10.3390/cells13242052
  4. Neuron. 2025 Jan 08. pii: S0896-6273(24)00885-7. [Epub ahead of print]113(1): 82-108
    Brain aging and rejuvenation at single-cell resolution.
    Eric D Sun, Rahul Nagvekar, Angela N Pogson, Anne Brunet.
      Brain aging leads to a decline in cognitive function and a concomitant increase in the susceptibility to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. A key question is how changes within individual cells of the brain give rise to age-related dysfunction. Developments in single-cell "omics" technologies, such as single-cell transcriptomics, have facilitated high-dimensional profiling of individual cells. These technologies have led to new and comprehensive characterizations of brain aging at single-cell resolution. Here, we review insights gleaned from single-cell omics studies of brain aging, starting with a cell-type-centric overview of age-associated changes and followed by a discussion of cell-cell interactions during aging. We highlight how single-cell omics studies provide an unbiased view of different rejuvenation interventions and comment on the promise of combinatorial rejuvenation approaches for the brain. Finally, we propose new directions, including models of brain aging and neural stem cells as a focal point for rejuvenation.
    Keywords:  aging; brain; cell-cell interactions; multi-omics; regeneration; rejuvenation; single-cell transcriptomics; spatial transcriptomics
    DOI:  https://doi.org/10.1016/j.neuron.2024.12.007
  5. Neurotherapeutics. 2025 Jan 06. pii: S1878-7479(24)00206-X. [Epub ahead of print] e00519
    Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.
    Hannah R Hudson, Xuehan Sun, Miranda E Orr.
      Cellular senescence is a cell state triggered by programmed physiological processes or cellular stress responses. Stress-induced senescent cells often acquire pathogenic traits, including a toxic secretome and resistance to apoptosis. When pathogenic senescent cells form faster than they are cleared by the immune system, they accumulate in tissues throughout the body and contribute to age-related diseases, including neurodegeneration. This review highlights evidence of pathogenic senescent cells in the brain and their role in Alzheimer's disease (AD), the leading cause of dementia in older adults. We also discuss the progress and challenges of senotherapies, pharmacological strategies to clear senescent cells or mitigate their toxic effects, which hold promise as interventions for AD and related dementias (ADRD).
    Keywords:  Alzheimer's disease; Biology of aging; Neurescence; Neurodegeneration; tau
    DOI:  https://doi.org/10.1016/j.neurot.2024.e00519
  6. MedComm (2020). 2025 Jan;6(1): e70030
    Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions.
    Tiantian Wang, Dong Zhou, Zhen Hong.
      Sarcopenia is defined as a muscle-wasting syndrome that occurs with accelerated aging, while cachexia is a severe wasting syndrome associated with conditions such as cancer and immunodeficiency disorders, which cannot be fully addressed through conventional nutritional supplementation. Sarcopenia can be considered a component of cachexia, with the bidirectional interplay between adipose tissue and skeletal muscle potentially serving as a molecular mechanism for both conditions. However, the underlying mechanisms differ. Recognizing the interplay and distinctions between these disorders is essential for advancing both basic and translational research in this area, enhancing diagnostic accuracy and ultimately achieving effective therapeutic solutions for affected patients. This review discusses the muscle microenvironment's changes contributing to these conditions, recent therapeutic approaches like lifestyle modifications, small molecules, and nutritional interventions, and emerging strategies such as gene editing, stem cell therapy, and gut microbiome modulation. We also address the challenges and opportunities of multimodal interventions, aiming to provide insights into the pathogenesis and molecular mechanisms of sarcopenia and cachexia, ultimately aiding in innovative strategy development and improved treatments.
    Keywords:  cachexia; molecules; pathogenesis; sarcopenia; targeted therapy
    DOI:  https://doi.org/10.1002/mco2.70030
  7. Biomedicines. 2024 Nov 28. pii: 2730. [Epub ahead of print]12(12):
    Targeting Mitochondria in Glioma: New Hopes for a Cure.
    Lidia Gatto, Vincenzo Di Nunno, Anna Ghelardini, Alicia Tosoni, Stefania Bartolini, Sofia Asioli, Stefano Ratti, Anna Luisa Di Stefano, Enrico Franceschi.
      Drugs targeting mitochondrial energy metabolism are emerging as promising antitumor therapeutics. Glioma treatment is extremely challenging due to the high complexity of the tumor and the high cellular heterogeneity. From a metabolic perspective, glioma cancer cells can be classified into the oxidative metabolic phenotype (mainly depending on mitochondrial respiration for energy production) and glycolytic phenotype or "Warburg effect" (mainly depending on glycolysis). Herein, we reviewed the function of novel bio-active molecules targeting oxidative phosphorylation (OXPHOS), mitochondrial membrane potential and mitochondrial dynamics. These molecules exhibit intriguing preclinical and clinical results and have been proven to be promising candidates to be further developed for glioma therapy. However, despite these initial encouraging results, it is imperative to rigorously assess the side effects of these metabolic drugs, which have a non-negligible toxicity profile.
    Keywords:  IACS-010759; ONC201; OXPHOS; Warburg; metformin; mitochondria
    DOI:  https://doi.org/10.3390/biomedicines12122730
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