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Autophagy, Cellular Senescence and Oxidative Stress in Ageing and Age-Related Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 May 2025) | Viewed by 8994

Special Issue Editor

Dr. Varvara Trachana

E-Mail Website
Guest Editor
Department of Biology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 415 00 Larissa, Greece
Interests: DNA damage; cellular senescence; cell cycle checkpoints; autophagy; age-related diseases; ageing; homeostasis; oxidative stress; macromolecular damage; cytotoxic stress
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ageing is a collection of functionality changes that lead to loss of homeostasis. This, at the organismal level, is demonstrated by several age-related diseases (diabetes, cardiovascular, neuro- or other degenerative diseases, cancer etc.). At the cellular level, there is an accumulation of macromolecular damage that can be mainly attributed to the age-driven augmentation of oxidative stress (OS). OS has long been implicated in senescence, which is also considered a basic contributor to age-related diseases’ etiopathogenesis. Autophagy, on the other hand, is a cytoprotective mechanism responsible for the removal of dysfunctional macromolecules/organelles. Due to the increase in life expectancy, the population affected by the aforementioned diseases has significantly increased. Therefore, there is an urgent need for studies that will shed light into the molecular network governing the relationships between OS, autophagy dysregulation and senescence onset, which in turn could lead to the identification of novel therapeutic approaches that will prove beneficial for the management of age-related diseases.

Dr. Varvara Trachana
Guest Editor

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Keywords

  • autophagy
  • oxidative stress
  • antioxidants
  • homeostasis
  • senescence
  • ageing
  • age-related diseases
  • reactive oxygen species
  • macromolecular damage
  • cytotoxic stress

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Published Papers (4 papers)

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Research

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16 pages, 2912 KiB  
Article
Exploring the Antioxidant Mechanisms of Nanoceria in Protecting HT22 Cells from Oxidative Stress
by Da-Long Dong and Guang-Zhen Jin
Int. J. Mol. Sci. 2024, 25(24), 13281; https://doi.org/10.3390/ijms252413281 - 11 Dec 2024
Cited by 1 | Viewed by 1004
Abstract
An excess of reactive oxygen species (ROS), leading to oxidative stress, is a major factor in aging. Antioxidant therapies are considered crucial for delaying aging. Nanoceria, a nanozyme with antioxidant activity, holds significant potential in protecting cells from oxidative stress-induced damage. This research [...] Read more.
An excess of reactive oxygen species (ROS), leading to oxidative stress, is a major factor in aging. Antioxidant therapies are considered crucial for delaying aging. Nanoceria, a nanozyme with antioxidant activity, holds significant potential in protecting cells from oxidative stress-induced damage. This research examines the neuroprotective role of nanoceria on HT22 cells subjected to oxidative stress induced by hydrogen peroxide (H2O2) and explores the associated molecular mechanisms. Our findings indicate that nanoceria enhances bcl-2 expression and significantly reduces Bax expression, resulting in an increased bcl-2/Bax ratio, which confirms its anti-apoptotic effect. Nanoceria boosts catalase expression and suppresses the p38 MAPK signaling pathway, indicating its role in shielding HT22 cells from oxidative stress damage induced by H2O2 through various protective mechanisms. These findings provide crucial experimental evidence for the potential applications of nanoceria in skin anti-aging and the prevention and treatment of other oxidative stress-related diseases. Full article
(This article belongs to the Special Issue Autophagy, Cellular Senescence and Oxidative Stress in Ageing and Age-Related Diseases)
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19 pages, 2877 KiB  
Article
Cryptomphalus aspersa Egg Extract Protects against Human Stem Cell Stress-Induced Premature Senescence
by Zozo Outskouni, Christina Christodoulou, Andreas Goutas, Ioannis D. Kyriazis, Adamantini Paraskevopoulou, George P. Laliotis, Anthia Matsakidou, Athanasios Gogas and Varvara Trachana
Int. J. Mol. Sci. 2024, 25(7), 3715; https://doi.org/10.3390/ijms25073715 - 27 Mar 2024
Cited by 1 | Viewed by 1605
Abstract
Cellular senescence is a tightly regulated pathophysiologic process and is caused by replicative exhaustion or external stressors. Since naturally derived bioactive compounds with anti-ageing properties have recently captured scientific interest, we analysed the anti-ageing and antioxidant efficacy of Cryptomphalus aspersa egg extract (CAEE). [...] Read more.
Cellular senescence is a tightly regulated pathophysiologic process and is caused by replicative exhaustion or external stressors. Since naturally derived bioactive compounds with anti-ageing properties have recently captured scientific interest, we analysed the anti-ageing and antioxidant efficacy of Cryptomphalus aspersa egg extract (CAEE). Its effects on stemness, wound-healing properties, antioxidant defense mechanisms, and DNA damage repair ability of Human Wharton’s jelly mesenchymal stem cells (WJ-MSCs) were analysed. Our results revealed that CAEE fortifies WJ-MSCs stemness, which possibly ameliorates their wound-healing ability. Additionally, we show that CAEE possesses a strong antioxidant capacity as demonstrated by the elevation of the levels of the basic antioxidant molecule, GSH, and the induction of the NRF2, a major antioxidant regulator. In addition, CAEE alleviated cells’ oxidative stress and therefore prevented stress-induced premature senescence (SIPS). Furthermore, we demonstrated that the prevention of SIPS could be mediated via the extract’s ability to induce autophagy, as indicated by the elevation of the protein levels of all basic autophagic molecules and the increase in formation of autophagolysosomes in CAEE-treated WJ-MSCs. Moreover, CAEE-treated cells exhibited decreased Caveolin-1 levels. We propose that Cryptomphalus aspersa egg extract comprises bioactive compounds that can demonstrate strong antioxidant/anti-ageing effects by regulating the Caveolin-1–autophagy–senescence molecular axis. Full article
(This article belongs to the Special Issue Autophagy, Cellular Senescence and Oxidative Stress in Ageing and Age-Related Diseases)
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19 pages, 7776 KiB  
Article
Ginsenoside F1-Mediated Telomere Preservation Delays Cellular Senescence
by Jingang Hou, Yeejin Yun, Byeongmin Jeon, Jongin Baek and Sunchang Kim
Int. J. Mol. Sci. 2023, 24(18), 14241; https://doi.org/10.3390/ijms241814241 - 19 Sep 2023
Cited by 5 | Viewed by 2940
Abstract
Telomeres play pivotal roles in processes closely related to somatic senescence and aging, making them a compelling target for interventions aimed at combating aging and age-related pathologies. Ginsenoside, a natural compound, has emerged as a potential remedy for promoting healthy aging, yet how [...] Read more.
Telomeres play pivotal roles in processes closely related to somatic senescence and aging, making them a compelling target for interventions aimed at combating aging and age-related pathologies. Ginsenoside, a natural compound, has emerged as a potential remedy for promoting healthy aging, yet how it protects telomeres remains incompletely understood. Here, we show that treatment of F1 can effectively restore the level of TRF2, thereby preserving telomere integrity. This restoration leads to inhibition of the DNA damage response and improvements in mitochondrial function and, ultimately, delays in cellular senescence. Conversely, depletion of TRF2 causes mitochondrial dysfunction, accompanied by increased oxidative stress, autophagy inhibition, insufficient energy metabolism, and the onset of cellular senescence. These observations underscore the critical role of TRF2 in maintaining telomere integrity and direct association with the initiation of cellular senescence. We conduct a further analysis, suggesting F1 could bind in proximity to the TRF2 heterodimer interface, potentially enhancing dimerization stability. These findings suggest that F1 may be a promising natural remedy for anti-aging, and restoring TRF2 could potentially prevent telomere-dependent diseases commonly associated with the aging process. Full article
(This article belongs to the Special Issue Autophagy, Cellular Senescence and Oxidative Stress in Ageing and Age-Related Diseases)
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Review

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21 pages, 2378 KiB  
Review
A Comprehensive Exploration of Caspase Detection Methods: From Classical Approaches to Cutting-Edge Innovations
by Mahmoud Zhra, Rani J. Qasem, Fai Aldossari, Rimah Saleem and Ahmad Aljada
Int. J. Mol. Sci. 2024, 25(10), 5460; https://doi.org/10.3390/ijms25105460 - 17 May 2024
Cited by 5 | Viewed by 2664
Abstract
The activation of caspases is a crucial event and an indicator of programmed cell death, also known as apoptosis. These enzymes play a central role in cancer biology and are considered one promising target for current and future advancements in therapeutic interventions. Traditional [...] Read more.
The activation of caspases is a crucial event and an indicator of programmed cell death, also known as apoptosis. These enzymes play a central role in cancer biology and are considered one promising target for current and future advancements in therapeutic interventions. Traditional methods of measuring caspase activity such as antibody-based methods provide fundamental insights into their biological functions, and are considered essential tools in the fields of cell and cancer biology, pharmacology and toxicology, and drug discovery. However, traditional methods, though extensively used, are now recognized as having various shortcomings. In addition, these methods fall short of providing solutions to and matching the needs of the rapid and expansive progress achieved in studying caspases. For these reasons, there has been a continuous improvement in detection methods for caspases and the network of pathways involved in their activation and downstream signaling. Over the past decade, newer methods based on cutting-edge state-of-the-art technologies have been introduced to the biomedical community. These methods enable both the temporal and spatial monitoring of the activity of caspases and their downstream substrates, and with enhanced accuracy and precision. These include fluorescent-labeled inhibitors (FLIs) for live imaging, single-cell live imaging, fluorescence resonance energy transfer (FRET) sensors, and activatable multifunctional probes for in vivo imaging. Recently, the recruitment of mass spectrometry (MS) techniques in the investigation of these enzymes expanded the repertoire of tools available for the identification and quantification of caspase substrates, cleavage products, and post-translational modifications in addition to unveiling the complex regulatory networks implicated. Collectively, these methods are enabling researchers to unravel much of the complex cellular processes involved in apoptosis, and are helping generate a clearer and comprehensive understanding of caspase-mediated proteolysis during apoptosis. Herein, we provide a comprehensive review of various assays and detection methods as they have evolved over the years, so to encourage further exploration of these enzymes, which should have direct implications for the advancement of therapeutics for cancer and other diseases. Full article
(This article belongs to the Special Issue Autophagy, Cellular Senescence and Oxidative Stress in Ageing and Age-Related Diseases)
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