bims-agimec Biomed News
on Aging mechanisms
Issue of 2024–12–01
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. Mitochondria: the epigenetic regulators of ovarian aging and longevity.
  2. The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.
  3. Molecular and Cellular Foundations of Aging of the Brain: Anti-aging Strategies in Alzheimer's Disease.
  4. Fecal Microbiota Transplantation, a tool to transfer healthy longevity.
  5. Circular RNAs as multifaceted molecular regulators of vital activity and potential biomarkers of aging.
  6. An Overview of the Genes and Biomarkers in Alzheimer's Disease.
  7. Mitochondria as sensors of intracellular pathogens.
  1. Front Endocrinol (Lausanne). 2024 ;15 1424826
    Mitochondria: the epigenetic regulators of ovarian aging and longevity.
    Shalini Mani, Vidushi Srivastava, Chesta Shandilya, Aditi Kaushik, Keshav K Singh.
      Ovarian aging is a major health concern for women. Ovarian aging is associated with reduced health span and longevity. Mitochondrial dysfunction is one of the hallmarks of ovarian aging. In addition to providing oocytes with optimal energy, the mitochondria provide a co-substrate that drives epigenetic processes. Studies show epigenetic alterations, both nuclear and mitochondrial contribute to ovarian aging. Both, nuclear and mitochondrial genomes cross-talk with each other, resulting in two ways orchestrated anterograde and retrograde response that involves epigenetic changes in nuclear and mitochondrial compartments. Epigenetic alterations causing changes in metabolism impact ovarian function. Key mitochondrial co-substrate includes acetyl CoA, NAD+, ATP, and α-KG. Thus, enhancing mitochondrial function in aging ovaries may preserve ovarian function and can lead to ovarian longevity and reproductive and better health outcomes in women. This article describes the role of mitochondria-led epigenetics involved in ovarian aging and discusses strategies to restore epigenetic reprogramming in oocytes by preserving, protecting, or promoting mitochondrial function.
    Keywords:  aging; epigenetics; menopause; mitochondria; ovary
    DOI:  https://doi.org/10.3389/fendo.2024.1424826
  2. Biomedicines. 2024 Nov 07. pii: 2540. [Epub ahead of print]12(11):
    The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.
    Vharoon Sharma Nunkoo, Alexander Cristian, Anamaria Jurcau, Razvan Gabriel Diaconu, Maria Carolina Jurcau.
      The impressive achievements made in the last century in extending the lifespan have led to a significant growth rate of elderly individuals in populations across the world and an exponential increase in the incidence of age-related conditions such as cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. To date, geroscientists have identified 12 hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, mitochondrial dysfunction, impaired nutrient sensing, cellular senescence, stem cell exhaustion, defective intercellular communication, chronic inflammation, and gut dysbiosis), intricately linked among each other, which can be targeted with senolytic or senomorphic drugs, as well as with more aggressive approaches such as cell-based therapies. To date, side effects seriously limit the use of these drugs. However, since rejuvenation is a dream of mankind, future research is expected to improve the tolerability of the available drugs and highlight novel strategies. In the meantime, the medical community, healthcare providers, and society should decide when to start these treatments and how to tailor them individually.
    Keywords:  aging; hallmarks of aging; neurodegeneration; rejuvenation; senolytics; senomorphics
    DOI:  https://doi.org/10.3390/biomedicines12112540
  3. Cell Mol Neurobiol. 2024 Nov 28. 44(1): 80
    Molecular and Cellular Foundations of Aging of the Brain: Anti-aging Strategies in Alzheimer's Disease.
    Magdalena Dziewa, Magdalena Złotek, Mariola Herbet, Iwona Piątkowska-Chmiel.
      Alzheimer's disease (AD) is a condition characterized by the gradual degeneration of the nervous system that poses significant challenges to cognitive function and overall mental health. Given the increasing global life expectancy, there is an urgent need for effective strategies to prevent and manage Alzheimer's disease, with a particular focus on anti-aging interventions. Recent scientific advancements have unveiled several promising strategies for combating Alzheimer's disease (AD), ranging from lifestyle interventions to cutting-edge pharmacological treatments and therapies targeting the underlying biological processes of aging and AD. Regular physical exercise, cognitive engagement, a balanced diet, and social interaction serve as key pillars in maintaining brain health. At the same time, therapies target key pathological mechanisms of AD, such as amyloid-beta accumulation, tau abnormalities, neuroinflammation, mitochondrial dysfunction, and synaptic loss, offering potential breakthroughs in treatment. Moreover, cutting-edge innovations such as gene therapy, stem cell transplantation, and novel drug delivery systems are emerging as potential game-changers in the fight against AD. This review critically evaluates the latest research on anti-aging interventions and their potential in preventing and treating Alzheimer's disease (AD) by exploring the connections between aging mechanisms and AD pathogenesis. It provides a comprehensive analysis of both well-established and emerging strategies, while also identifying key gaps in current knowledge to guide future research efforts.
    Keywords:  Alzheimer’s disease; Anti-aging interventions; Cell based-therapy; Cellular aging; Gene therapy; Lifestyle interventions
    DOI:  https://doi.org/10.1007/s10571-024-01514-0
  4. Ageing Res Rev. 2024 Nov 23. pii: S1568-1637(24)00403-3. [Epub ahead of print] 102585
    Fecal Microbiota Transplantation, a tool to transfer healthy longevity.
    Marta G Novelle, Beatriz Naranjo, Juan L López-Cánovas, Alberto Díaz-Ruiz.
      The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.
    Keywords:  FMT-concerns; aging; fecal microbiota transplantation; gut-microbiome; longevity
    DOI:  https://doi.org/10.1016/j.arr.2024.102585
  5. Epigenomics. 2024 Nov 26. 1-11
    Circular RNAs as multifaceted molecular regulators of vital activity and potential biomarkers of aging.
    Anna-Maria D Zharova, Alexey D Perenkov, Maria V Vedunova.
      Aging presents a significant challenge to health and social care systems due to the increasing proportion of the elderly population. The identification of reliable biomarkers to assess the progression of aging remains an unresolved question. Circular RNAs (circRNAs) are single-stranded covalently closed RNAs. They have been found to regulate various biological processes. CircRNAs are present in human biological fluids, are relatively stable, and accumulate with age, making them promising as biomarkers of aging. Current information on the expression of circRNAs in aging was analyzed using scientific databases. In this review, we have identified key stages in the study of circRNAs during aging and summarized the current understanding of their biogenesis. By focusing on the role of circRNAs in processes that contribute to aging - such as genomic stability, metabolism, cell death, and signaling pathways - we hypothesize that circRNAs may drive the aging process through their age-related accumulation and resultant deregulation. Examples of age-related differential expression of circRNAs in various species, including humans, are provided. This review highlights the importance of finding novel epigenetic biomarkers of aging, beyond the already identified molecules (circFOXO3, circRNA100783, circPVT1), and highlights circRNAs as a potential therapeutic target for the treatment of age-associated diseases.
    Keywords:  aging; biomarkers; circRNA; elderly population; lifespan; ncRNA; splicing
    DOI:  https://doi.org/10.1080/17501911.2024.2430165
  6. Ageing Res Rev. 2024 Nov 27. pii: S1568-1637(24)00417-3. [Epub ahead of print] 102599
    An Overview of the Genes and Biomarkers in Alzheimer's Disease.
    Hari Krishnan Krishnamurthy, Vasanth Jayaraman, Karthik Krishna, Tianhao Wang, Kang Bei, Chithra Changalath, John J Rajasekaran.
      Alzheimer's disease (AD) is the most common type of dementia and neurodegenerative disease characterized by neurofibrillary tangles (NFTs) and amyloid plaque. Familial AD is caused by mutations in the APP, PSEN1, and PSEN2 genes and these mutations result in the early onset of the disease. Sporadic AD usually affects older adults over the age of 65 years and is, therefore classified as late-onset AD (LOAD). Several risk factors associated with LOAD including the APOE gene have been identified. Moreover, GWAS studies have identified a wide array of genes and polymorphisms that are associated with LOAD risk. Currently, the diagnosis of AD involves the evaluation of memory and personality changes, cognitive impairment, and medical and family history to rule out other diseases. Laboratory tests to assess the biomarkers in the body fluids as well as MRI, CT, and PET scans to analyze the presence of plaques and NFTs are also included in the diagnosis of AD. It is important to diagnose AD before the onset of clinical symptoms, i.e. during the preclinical stage, to delay the progression and for better management of the disease. Research has been conducted to identify biomarkers of AD in the CSF, serum, saliva, and urine during the preclinical stage. Current research has identified several biomarkers and potential biomarkers in the body fluids that enhance diagnostic accuracy. Aside from genetics, other factors such as diet, physical activity, and lifestyle factors may influence the risk of developing AD. Clinical trials are underway to find potential biomarkers, diagnostic measures, and treatments for AD mainly in the preclinical stage. This review provides an overview of the genes and biomarkers of AD.
    Keywords:  Alzheimer’s disease; amyloid plaque; biomarker; neurofibrillary tangles; preclinical; preventive measures
    DOI:  https://doi.org/10.1016/j.arr.2024.102599
  7. Trends Endocrinol Metab. 2024 Nov 22. pii: S1043-2760(24)00291-1. [Epub ahead of print]
    Mitochondria as sensors of intracellular pathogens.
    Jose M Delgado, Lena Pernas.
      Mitochondria must sense their environment to enable cells and organisms to adapt to diverse environments and survive during stress. However, during microbial infection, an evolutionary pressure since the inception of the eukaryotic cell, these organelles are traditionally viewed as targets for microbes. In this opinion we consider the perspective that mitochondria are domesticated microbes that sense and guard their 'host' cell against pathogens. We explore potential mechanisms by which mitochondria detect intracellular pathogens and induce mitochondria-autonomous responses that activate cellular defenses.
    Keywords:  MAVS; PAMPs; domesticated microbes; import receptors; microbial sensors; mitochondria
    DOI:  https://doi.org/10.1016/j.tem.2024.10.009
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