bims-agimec Biomed News
on Aging mechanisms
Issue of 2024–07–21
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. Mitochondrial dysfunction and its association with age-related disorders.
  2. Vascular Aging in Ischemic Stroke.
  3. Immune surveillance of senescence: potential application to age-related diseases.
  4. Targeting neuronal epigenomes for brain rejuvenation.
  5. Pathological mechanisms of kidney disease in ageing.
  6. The role of SIRT1 in kidney diseases.
  7. MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.
  1. Front Physiol. 2024 ;15 1384966
    Mitochondrial dysfunction and its association with age-related disorders.
    Indumathi Somasundaram, Samatha M Jain, Marcel Blot-Chabaud, Surajit Pathak, Antara Banerjee, Sonali Rawat, Neeta Raj Sharma, Asim K Duttaroy.
      Aging is a complex process that features a functional decline in many organelles. Various factors influence the aging process, such as chromosomal abnormalities, epigenetic changes, telomere shortening, oxidative stress, and mitochondrial dysfunction. Mitochondrial dysfunction significantly impacts aging because mitochondria regulate cellular energy, oxidative balance, and calcium levels. Mitochondrial integrity is maintained by mitophagy, which helps maintain cellular homeostasis, prevents ROS production, and protects against mtDNA damage. However, increased calcium uptake and oxidative stress can disrupt mitochondrial membrane potential and permeability, leading to the apoptotic cascade. This disruption causes increased production of free radicals, leading to oxidative modification and accumulation of mitochondrial DNA mutations, which contribute to cellular dysfunction and aging. Mitochondrial dysfunction, resulting from structural and functional changes, is linked to age-related degenerative diseases. This review focuses on mitochondrial dysfunction, its implications in aging and age-related disorders, and potential anti-aging strategies through targeting mitochondrial dysfunction.
    Keywords:  ROS production; chromosomal aberrations; mitochondrial DNA; mitochondrial dysfunction; mitophagy
    DOI:  https://doi.org/10.3389/fphys.2024.1384966
  2. J Am Heart Assoc. 2024 Jul 18. e033341
    Vascular Aging in Ischemic Stroke.
    Lian Liu, Bo Zhao, Yueyang Yu, Wenwei Gao, Weitu Liu, Lili Chen, Zhongyuan Xia, Quan Cao.
      Cellular senescence, a permanent halt in cell division due to stress, spurs functional and structural changes, contributing to vascular aging characterized by endothelial dysfunction and vascular remodeling. This process raises the risk of ischemic stroke (IS) in older individuals, with its mechanisms still not completely understood despite ongoing research efforts. In this review, we have analyzed the impact of vascular aging on increasing susceptibility and exacerbating the pathology of IS. We have emphasized the detrimental effects of endothelial dysfunction and vascular remodeling influenced by oxidative stress and inflammatory response on vascular aging and IS. Our goal is to aid the understanding of vascular aging and IS pathogenesis, particularly benefiting older adults with high risk of IS.
    Keywords:  endothelial dysfunction; ischemic stroke; vascular aging; vascular remodeling
    DOI:  https://doi.org/10.1161/JAHA.123.033341
  3. Trends Cell Biol. 2024 Jul 17. pii: S0962-8924(24)00121-1. [Epub ahead of print]
    Immune surveillance of senescence: potential application to age-related diseases.
    Teh-Wei Wang, Makoto Nakanishi.
      Several lines of evidence suggest that the age-dependent accumulation of senescent cells leads to chronic tissue microinflammation, which in turn contributes to age-related pathologies. In general, senescent cells can be eliminated by the host's innate and adaptive immune surveillance system, including macrophages, NK cells, and T cells. Impaired immune surveillance leads to the accumulation of senescent cells and accelerates the aging process. Recently, senescent cells, like cancer cells, have been shown to express certain types of immune checkpoint proteins as well as non-classical immune-tolerant MHC variants, leading to immune escape from surveillance systems. Thus, immune checkpoint blockade (ICB) may be a promising strategy to enhance immune surveillance of senescence, leading to the amelioration of some age-related diseases and tissue dysfunction.
    Keywords:  immune checkpoint blockade; immune clearance; senescence
    DOI:  https://doi.org/10.1016/j.tcb.2024.06.007
  4. EMBO J. 2024 Jul 15.
    Targeting neuronal epigenomes for brain rejuvenation.
    Sara Zocher.
      Aging is associated with a progressive decline of brain function, and the underlying causes and possible interventions to prevent this cognitive decline have been the focus of intense investigation. The maintenance of neuronal function over the lifespan requires proper epigenetic regulation, and accumulating evidence suggests that the deterioration of the neuronal epigenetic landscape contributes to brain dysfunction during aging. Epigenetic aging of neurons may, however, be malleable. Recent reports have shown age-related epigenetic changes in neurons to be reversible and targetable by rejuvenation strategies that can restore brain function during aging. This review discusses the current evidence that identifies neuronal epigenetic aging as a driver of cognitive decline and a promising target of brain rejuvenation strategies, and it highlights potential approaches for the specific manipulation of the aging neuronal epigenome to restore a youthful epigenetic state in the brain.
    Keywords:  Cognitive Decline; Epigenetic Rejuvenation; Epigenome Editing; Neuron Aging; Neuronal Epigenome
    DOI:  https://doi.org/10.1038/s44318-024-00148-8
  5. Nat Rev Nephrol. 2024 Jul 18.
    Pathological mechanisms of kidney disease in ageing.
    Takeshi Yamamoto, Yoshitaka Isaka.
      The kidney is a metabolically active organ that requires energy to drive processes such as tubular reabsorption and secretion, and shows a decline in function with advancing age. Various molecular mechanisms, including genomic instability, telomere attrition, inflammation, autophagy, mitochondrial function, and changes to the sirtuin and Klotho signalling pathways, are recognized regulators of individual lifespan and pivotal factors that govern kidney ageing. Thus, mechanisms that contribute to ageing not only dictate renal outcomes but also exert a substantial influence over life expectancy. Conversely, kidney dysfunction, in the context of chronic kidney disease (CKD), precipitates an expedited ageing trajectory in individuals, leading to premature ageing and a disconnect between biological and chronological age. As CKD advances, age-related manifestations such as frailty become increasingly conspicuous. Hence, the pursuit of healthy ageing necessitates not only the management of age-related complications but also a comprehensive understanding of the processes and markers that underlie systemic ageing. Here, we examine the hallmarks of ageing, focusing on the mechanisms by which they affect kidney health and contribute to premature organ ageing. We also review diagnostic methodologies and interventions for premature ageing, with special consideration given to the potential of emerging therapeutic avenues to target age-related kidney diseases.
    DOI:  https://doi.org/10.1038/s41581-024-00868-4
  6. Int Urol Nephrol. 2024 Jul 19.
    The role of SIRT1 in kidney diseases.
    Wei Wang, Yuanyuan Hu, Ning Ding, Jiping Wei, Cairong Li.
      SIRT1, a nicotinamide adenine dinucleotide (NAD +)-dependent class III histone deacetylase, exhibits a high level of expression within renal tissues. It has garnered considerable recognition for its pivotal role in modulating signaling pathways intricately linked with the aging process; however, it extends beyond this in the organism. The literature reports that SIRT1 regulates biological processes such as glucose metabolism, lipid metabolism, oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and apoptosis. Therefore, our study reviews the primary mechanisms by which SIRT1 induces kidney disease and the regulation of related signaling pathways in different models of renal disease. We also discuss commonly studied SIRT1-targeted interventional drugs reported in the literature, including inhibitors (e.g., Ex-527) and activators (e.g., resveratrol). This study aims to provide theoretical foundations and clinical insights for the development and screening of clinical drugs targeting SIRT1, aiming at enhanced scientific approaches for the prevention and treatment of kidney diseases.
    Keywords:  Interventional drugs; Kidney diseases; Mechanism; NAD+; SIRT1
    DOI:  https://doi.org/10.1007/s11255-024-04162-x
  7. Neurochem Res. 2024 Jul 13.
    MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.
    Jian-Sheng Luo, Wen-Hu Zhai, Ling-Ling Ding, Xian-Jie Zhang, Jia Han, Jia-Qi Ning, Xue-Meng Chen, Wen-Cai Jiang, Ru-Yu Yan, Meng-Jie Chen.
      Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control.
    Keywords:  Alzheimer’s disease; MAMs; Mitochondrial quality control
    DOI:  https://doi.org/10.1007/s11064-024-04205-w
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