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Molecular Biology of Senescence
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Molecular Biology of Senescence

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 21326

Special Issue Editor

Dr. Nicola Alessio

E-Mail Website
Guest Editor
Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Interests: stem cells; cell therapy; secretome; extracellular-vesicle; exosomes; differentiation; inflammation; diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Senescence is the process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing cell death. The word senescence can refer to either cellular senescence or to aging of the whole organism. Several studies correlate cellular senescence to aging, as it largely contributes to reducing tissue functions and renewal. On the other side, it is also believed to promote protective anticancer mechanisms leading to tumor growth arrest or, paradoxically, the persistence of senescent cells in tissues that may promote cancer onset. 

IJMS sets up this Special Issue focusing on the current understanding and future research directions regarding the molecular mechanisms of senescence and the related disease. We warmly welcome original research article and review articles relating to this hot topic.

Dr. Nicola Alessio
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cellular senescence
  • aging
  • delaying senescence
  • aging-associated diseases

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Published Papers (5 papers)

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Research

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15 pages, 9271 KiB  
Article
Mesenchymal Stem Cell Behavior under Microgravity: From Stress Response to a Premature Senescence
by Renzo Pala, Sara Cruciani, Alessia Manca, Giuseppe Garroni, Mohammed Amine EL Faqir, Veronica Lentini, Giampiero Capobianco, Antonella Pantaleo and Margherita Maioli
Int. J. Mol. Sci. 2023, 24(9), 7753; https://doi.org/10.3390/ijms24097753 - 24 Apr 2023
Cited by 6 | Viewed by 2347
Abstract
Mesenchymal stem cells are undifferentiated cells able to acquire different phenotypes under specific stimuli. Wharton’s jelly is a tissue in the umbilical cord that contains mesenchymal stromal cells (MSCs) with a high plasticity and differentiation potential. Their regeneration capability is compromised by cell [...] Read more.
Mesenchymal stem cells are undifferentiated cells able to acquire different phenotypes under specific stimuli. Wharton’s jelly is a tissue in the umbilical cord that contains mesenchymal stromal cells (MSCs) with a high plasticity and differentiation potential. Their regeneration capability is compromised by cell damage and aging. The main cause of cell damage is oxidative stress coming from an imbalance between oxidant and antioxidant species. Microgravity represents a stressing condition able to induce ROS production, ultimately leading to different subcellular compartment damages. Here, we analyzed molecular programs of stemness (Oct-4; SOX2; Nanog), cell senescence, p19, p21 (WAF1/CIP1), p53, and stress response in WJ-MSCs exposed to microgravity. From our results, we can infer that a simulated microgravity environment is able to influence WJ-MSC behavior by modulating the expression of stress and stemness-related genes, cell proliferation regulators, and both proapoptotic and antiapoptotic genes. Our results suggest a cellular adaptation addressed to survival occurring during the first hours of simulated microgravity, followed by a loss of stemness and proliferation capability, probably related to the appearance of a molecular program of senescence. Full article
(This article belongs to the Special Issue Molecular Biology of Senescence)
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10 pages, 2819 KiB  
Communication
New Senolysis Approach via Antibody–Drug Conjugate Targeting of the Senescent Cell Marker Apolipoprotein D for Skin Rejuvenation
by Kento Takaya, Toru Asou and Kazuo Kishi
Int. J. Mol. Sci. 2023, 24(6), 5857; https://doi.org/10.3390/ijms24065857 - 20 Mar 2023
Cited by 5 | Viewed by 2583
Abstract
Senescent cells accumulate in aging skin, causing age-related changes and a decline in functional efficiency. Therefore, senolysis, a treatment that specifically removes senescent cells and rejuvenates the skin, should be explored. We targeted apolipoprotein D (ApoD), a previously identified marker expressed on senescent [...] Read more.
Senescent cells accumulate in aging skin, causing age-related changes and a decline in functional efficiency. Therefore, senolysis, a treatment that specifically removes senescent cells and rejuvenates the skin, should be explored. We targeted apolipoprotein D (ApoD), a previously identified marker expressed on senescent dermal fibroblasts, and investigated a novel senolysis approach using a monoclonal antibody against this antigen and a secondary antibody conjugated with the cytotoxic drug pyrrolobenzodiazepine. Observations using fluorescently labeled antibodies revealed that ApoD functions as a surface marker of senescent cells and that the antibody is taken up and internalized only by such cells. The concurrent administration of the antibody with the PBD-conjugated secondary antibody specifically eliminated only senescent cells without harming young cells. The antibody–drug conjugate treatment of aging mice combined with the administration of antibodies reduced the number of senescent cells in the dermis of mice and improved the senescent skin phenotype. These results provide a proof-of-principle evaluation of a novel approach to specifically eliminate senescent cells using antibody–drug conjugates against senescent cell marker proteins. This approach is a potential candidate for clinical applications to treat pathological skin aging and related diseases via the removal of senescent cells. Full article
(This article belongs to the Special Issue Molecular Biology of Senescence)
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11 pages, 1735 KiB  
Article
Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3
by Kento Takaya, Toru Asou and Kazuo Kishi
Int. J. Mol. Sci. 2022, 23(12), 6531; https://doi.org/10.3390/ijms23126531 - 10 Jun 2022
Cited by 8 | Viewed by 3025
Abstract
The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens [...] Read more.
The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens that are specifically expressed on senescent cells for their selective elimination. We showed that atypical chemokine receptor 3 (ACKR3), a receptor of the CXC motif chemokine 12 (CXCL12) implicated in cancer, inflammation, and cardiovascular disorders, is selectively expressed on the surface of senescent human fibroblasts but not on proliferating cells. Importantly, the differential presence of ACKR3 enabled the isolation of senescent cells by flow cytometry using anti-ACKR3 antibodies. Furthermore, antibody-dependent cellular cytotoxicity assays revealed that cell surface ACKR3 preferentially sensitizes senescent but not dividing fibroblasts to cell injury by natural killer cells. Conclusively, the selective expression of ACKR3 on the surface of senescent cells allows the preferential elimination of senescent cells. These results might contribute to the future development of novel senolysis approaches. Full article
(This article belongs to the Special Issue Molecular Biology of Senescence)
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Review

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31 pages, 1595 KiB  
Review
Integrated Stress Response (ISR) Pathway: Unraveling Its Role in Cellular Senescence
by Alexander Kalinin, Ekaterina Zubkova and Mikhail Menshikov
Int. J. Mol. Sci. 2023, 24(24), 17423; https://doi.org/10.3390/ijms242417423 - 13 Dec 2023
Cited by 2 | Viewed by 5917
Abstract
Cellular senescence is a complex process characterized by irreversible cell cycle arrest. Senescent cells accumulate with age, promoting disease development, yet the absence of specific markers hampers the development of selective anti-senescence drugs. The integrated stress response (ISR), an evolutionarily highly conserved signaling [...] Read more.
Cellular senescence is a complex process characterized by irreversible cell cycle arrest. Senescent cells accumulate with age, promoting disease development, yet the absence of specific markers hampers the development of selective anti-senescence drugs. The integrated stress response (ISR), an evolutionarily highly conserved signaling network activated in response to stress, globally downregulates protein translation while initiating the translation of specific protein sets including transcription factors. We propose that ISR signaling plays a central role in controlling senescence, given that senescence is considered a form of cellular stress. Exploring the intricate relationship between the ISR pathway and cellular senescence, we emphasize its potential as a regulatory mechanism in senescence and cellular metabolism. The ISR emerges as a master regulator of cellular metabolism during stress, activating autophagy and the mitochondrial unfolded protein response, crucial for maintaining mitochondrial quality and efficiency. Our review comprehensively examines ISR molecular mechanisms, focusing on ATF4-interacting partners, ISR modulators, and their impact on senescence-related conditions. By shedding light on the intricate relationship between ISR and cellular senescence, we aim to inspire future research directions and advance the development of targeted anti-senescence therapies based on ISR modulation. Full article
(This article belongs to the Special Issue Molecular Biology of Senescence)
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18 pages, 2063 KiB  
Review
Extracellular Vesicles as “Very Important Particles” (VIPs) in Aging
by Cristina Mas-Bargues and Matilde Alique
Int. J. Mol. Sci. 2023, 24(4), 4250; https://doi.org/10.3390/ijms24044250 - 20 Feb 2023
Cited by 13 | Viewed by 6006
Abstract
In recent decades, extracellular vesicles have been recognized as “very important particles” (VIPs) associated with aging and age-related disease. During the 1980s, researchers discovered that these vesicle particles released by cells were not debris but signaling molecules carrying cargoes that play key roles [...] Read more.
In recent decades, extracellular vesicles have been recognized as “very important particles” (VIPs) associated with aging and age-related disease. During the 1980s, researchers discovered that these vesicle particles released by cells were not debris but signaling molecules carrying cargoes that play key roles in physiological processes and physiopathological modulation. Following the International Society for Extracellular Vesicles (ISEV) recommendation, different vesicle particles (e.g., exosomes, microvesicles, oncosomes) have been named globally extracellular vesicles. These vesicles are essential to maintain body homeostasis owing to their essential and evolutionarily conserved role in cellular communication and interaction with different tissues. Furthermore, recent studies have shown the role of extracellular vesicles in aging and age-associated diseases. This review summarizes the advances in the study of extracellular vesicles, mainly focusing on recently refined methods for their isolation and characterization. In addition, the role of extracellular vesicles in cell signaling and maintenance of homeostasis, as well as their usefulness as new biomarkers and therapeutic agents in aging and age-associated diseases, has also been highlighted. Full article
(This article belongs to the Special Issue Molecular Biology of Senescence)
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