Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Cellular Senescence in Physiological and Pathological Processes
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Cellular Senescence in Physiological and Pathological Processes

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 (31 May 2022) | Viewed by 28498

Special Issue Editors

Dr. Tiziana Squillaro

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, Medical School, University of Naples Federico II, Via Pansini, 80131 Naples, Italy
Interests: stem cells; cell culture; apoptosis; authophagy
Special Issues, Collections and Topics in MDPI journals
Dr. Mauro Finicelli

E-Mail Website
Guest Editor
Research Institute on Terrestrial Ecosystems (IRET), National Research Council of Italy (CNR), Via Pietro Castellino 111, 80131 Naples, Italy
Interests: stem cell; bioactive molecules; pulmonary disease; aging related disease; senescence; miRNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Senescence is the permanent cell cycle arrest that occurs in response to extracellular or intracellular stress. It determines the loss of cellular functions over time. A senescent cell loses its original function and acquires new activities. Senescent cells secrete senescence-associated secretory phenotype (SASP) proteins to carry out several functions such as sensitizing normal neighboring cells to senesce, reinforcing the senescence process through autocrine signaling, inducing tissue remodeling and repair, and promoting wound healing and immune cell recruitment. Cellular senescence is also believed to promote protective anticancer mechanisms resulting in tumor growth arrest or, paradoxically, persistence of senescent cells in tissues may promote cancer onset. In addition, numerous studies correlate cellular senescence to aging, as it limits the proliferation of damaged cells largely contributing to the reduction in tissue functions and renewal. Senescence has also been indicated as a major cause of age-related diseases. Recent evidence has shown that pharmacological ablation of senescent cells improves longevity and promotes health span.

This Special issue welcomes original research and critical review on the role of cellular senescence in physiological and pathological processes. Topics of this Special Issue include but are not limited to regulatory pathways of senescence; senescence and stem cells; links between cellular senescence and aging; novel therapeutic treatment to remove senescent cells; and senescence and cancer.

Dr. Tiziana Squillaro
Dr. Mauro Finicelli
Guest Editors

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

  • replicative senescence
  • aging
  • aging-related disease
  • senescence-associated secretory phenotype (SASP)
  • senolytic drugs
  • senotherapies
  • senescence in cancer

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

30 pages, 6122 KiB  
Article
Modeling of the Senescence-Associated Phenotype in Human Skin Fibroblasts
by Marta Gerasymchuk, Gregory Ian Robinson, Olga Kovalchuk and Igor Kovalchuk
Int. J. Mol. Sci. 2022, 23(13), 7124; https://doi.org/10.3390/ijms23137124 - 27 Jun 2022
Cited by 13 | Viewed by 4239
Abstract
Modern understanding of aging is based on the accumulation of cellular damage during one’s life span due to the gradual deterioration of regenerative mechanisms in response to the continuous effect of stress, lifestyle, and environmental factors, followed by increased morbidity and mortality. Simultaneously, [...] Read more.
Modern understanding of aging is based on the accumulation of cellular damage during one’s life span due to the gradual deterioration of regenerative mechanisms in response to the continuous effect of stress, lifestyle, and environmental factors, followed by increased morbidity and mortality. Simultaneously, the number of senescent cells accumulate exponentially as organisms age. Cell culture models are valuable tools to investigate the mechanisms of aging by inducing cellular senescence in stress-induced premature senescence (SIPS) models. Here, we explain the three-step and one-step H2O2-induced senescence models of SIPS designed and reproduced on different human dermal fibroblast cell lines (CCD-1064Sk, CCD-1135Sk, and BJ-5ta). In both SIPS models, it was evident that the fibroblasts developed similar aging characteristics as cells with replicative senescence. Among the most noticeable senescent biomarkers were increased β-Gal expression, high levels of the p21 protein, altered levels of cell-cycle regulators (i.e., CDK2 and c-Jun), compromised extracellular matrix (ECM) composition, reduced cellular viability, and delayed wound healing properties. Based on the significant increase in senescence biomarkers in fibroblast cultures, reduced functional activity, and metabolic dysfunction, the one-step senescence model was chosen as a feasible and reliable method for future testing of anti-aging compounds. Full article
(This article belongs to the Special Issue Cellular Senescence in Physiological and Pathological Processes)
►▼ Show Figures

Figure 1

22 pages, 4745 KiB  
Article
Biochemical and Cellular Characterization of New Radio-Resistant Cell Lines Reveals a Role of Natural Flavonoids to Bypass Senescence
by Maria Russo, Carmela Spagnuolo, Stefania Moccia, Idolo Tedesco, Fabio Lauria and Gian Luigi Russo
Int. J. Mol. Sci. 2022, 23(1), 301; https://doi.org/10.3390/ijms23010301 - 28 Dec 2021
Cited by 7 | Viewed by 2488
Abstract
Cancer is one of the main causes of death worldwide, and, among the most frequent cancer types, osteosarcoma accounts for 56% of bone neoplasms observed in children and colorectal cancer for 10.2% of tumors diagnosed in the adult population. A common and frequent [...] Read more.
Cancer is one of the main causes of death worldwide, and, among the most frequent cancer types, osteosarcoma accounts for 56% of bone neoplasms observed in children and colorectal cancer for 10.2% of tumors diagnosed in the adult population. A common and frequent hurdle in cancer treatment is the emergence of resistance to chemo- and radiotherapy whose biological causes are largely unknown. In the present work, human osteosarcoma (SAOS) and colorectal adenocarcinoma (HT29) cell lines were γ-irradiated at doses mimicking the sub-lethal irradiation in clinical settings to obtain two radio-resistant cellular sub-populations named SAOS400 and HT500, respectively. Since “therapy-induced senescence” (TIS) is often associated with tumor response to radiotherapy in cancer cells, we measured specific cellular and biochemical markers of senescence in SAOS400 and HT500 cells. In detail, both cell lines were characterized by a higher level of expression of cyclin-dependent kinase inhibitors p16INK4 and p21CIP1 and increased positivity to SAβ-gal (senescence-associated β-galactosidase) with respect to parental cells. Moreover, the intracellular levels of reactive oxygen species in the resistant cells were significantly lower compared to the parental counterparts. Subsequently, we demonstrated that senolytic agents were able to sensitize SAOS400 and HT500 to cell death induced by γ-irradiation. Employing two natural flavonoids, fisetin and quercetin, and a BH3-mimetic, ABT-263/navitoclax, we observed that their association with γ-irradiation significantly reduced the expression of p16INK4, p21CIP1 and synergistically (combination index < 1) increased cell death compared to radiation mono-alone treatments. The present results reinforce the potential role of senolytics as adjuvant agents in cancer therapy. Full article
(This article belongs to the Special Issue Cellular Senescence in Physiological and Pathological Processes)
►▼ Show Figures

Figure 1

Review

Jump to: Research, Other

24 pages, 2208 KiB  
Review
In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression
by Myriam Janeth Salazar-Terreros and Jean-Paul Vernot
Int. J. Mol. Sci. 2022, 23(13), 7350; https://doi.org/10.3390/ijms23137350 - 01 Jul 2022
Cited by 6 | Viewed by 3085
Abstract
Cellular senescence is recognized as a dynamic process in which cells evolve and adapt in a context dependent manner; consequently, senescent cells can exert both beneficial and deleterious effects on their surroundings. Specifically, senescent mesenchymal stromal cells (MSC) in the bone marrow (BM) [...] Read more.
Cellular senescence is recognized as a dynamic process in which cells evolve and adapt in a context dependent manner; consequently, senescent cells can exert both beneficial and deleterious effects on their surroundings. Specifically, senescent mesenchymal stromal cells (MSC) in the bone marrow (BM) have been linked to the generation of a supporting microenvironment that enhances malignant cell survival. However, the study of MSC’s senescence role in leukemia development has been straitened not only by the availability of suitable models that faithfully reflect the structural complexity and biological diversity of the events triggered in the BM, but also by the lack of a universal, standardized method to measure senescence. Despite these constraints, two- and three dimensional in vitro models have been continuously improved in terms of cell culture techniques, support materials and analysis methods; in addition, research on animal models tends to focus on the development of techniques that allow tracking leukemic and senescent cells in the living organism, as well as to modify the available mice strains to generate individuals that mimic human BM characteristics. Here, we present the main advances in leukemic niche modeling, discussing advantages and limitations of the different systems, focusing on the contribution of senescent MSC to leukemia progression. Full article
(This article belongs to the Special Issue Cellular Senescence in Physiological and Pathological Processes)
►▼ Show Figures

Figure 1

15 pages, 3119 KiB  
Review
Age-Related Changes in the Fibroblastic Differon of the Dermis: Role in Skin Aging
by Alla Zorina, Vadim Zorin, Dmitry Kudlay and Pavel Kopnin
Int. J. Mol. Sci. 2022, 23(11), 6135; https://doi.org/10.3390/ijms23116135 - 30 May 2022
Cited by 15 | Viewed by 3319
Abstract
Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been [...] Read more.
Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been revealed that the amount of fibroblasts decreases markedly with age and their functional activity is also reduced. This inevitably leads to a decrease in the regenerative abilities of the skin and the progression of its aging. In this review we consider the mechanisms underlying these processes, mainly the changes observed with age in the stem/progenitor cells that constitute the fibroblastic differon of the dermis and form their microenvironment (niches). These changes lead to the depletion of stem cells, which, in turn, leads to a decrease in the number of differentiated (mature) dermal fibroblasts responsible for the production of the dermal extracellular matrix and its remodeling. We also describe in detail DNA damages, their cellular and systemic consequences, molecular mechanisms of DNA damage response, and also the role of fibroblast senescence in skin aging. Full article
(This article belongs to the Special Issue Cellular Senescence in Physiological and Pathological Processes)
►▼ Show Figures

Figure 1

16 pages, 874 KiB  
Review
Aging, Cellular Senescence, and Alzheimer’s Disease
by Rui-Ming Liu
Int. J. Mol. Sci. 2022, 23(4), 1989; https://doi.org/10.3390/ijms23041989 - 11 Feb 2022
Cited by 79 | Viewed by 11612
Abstract
Aging is the greatest risk factor for late-onset Alzheimer’s disease (LOAD), which accounts for >95% of Alzheimer’s disease (AD) cases. The mechanism underlying the aging-related susceptibility to LOAD is unknown. Cellular senescence, a state of permanent cell growth arrest, is believed to contribute [...] Read more.
Aging is the greatest risk factor for late-onset Alzheimer’s disease (LOAD), which accounts for >95% of Alzheimer’s disease (AD) cases. The mechanism underlying the aging-related susceptibility to LOAD is unknown. Cellular senescence, a state of permanent cell growth arrest, is believed to contribute importantly to aging and aging-related diseases, including AD. Senescent astrocytes, microglia, endothelial cells, and neurons have been detected in the brain of AD patients and AD animal models. Removing senescent cells genetically or pharmacologically ameliorates β-amyloid (Aβ) peptide and tau-protein-induced neuropathologies, and improves memory in AD model mice, suggesting a pivotal role of cellular senescence in AD pathophysiology. Nonetheless, although accumulated evidence supports the role of cellular senescence in aging and AD, the mechanisms that promote cell senescence and how senescent cells contribute to AD neuropathophysiology remain largely unknown. This review summarizes recent advances in this field. We believe that the removal of senescent cells represents a promising approach toward the effective treatment of aging-related diseases, such as AD. Full article
(This article belongs to the Special Issue Cellular Senescence in Physiological and Pathological Processes)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

30 pages, 4362 KiB  
Protocol
Optimized Protocol for Proportionate CNS Cell Retrieval as a Versatile Platform for Cellular and Molecular Phenomapping in Aging and Neurodegeneration
by Quratul Ain, Christian W. Schmeer, Diane Wengerodt, Yvonne Hofmann, Otto W. Witte and Alexandra Kretz
Int. J. Mol. Sci. 2022, 23(6), 3000; https://doi.org/10.3390/ijms23063000 - 10 Mar 2022
Cited by 1 | Viewed by 2365
Abstract
Efficient purification of viable neural cells from the mature CNS has been historically challenging due to the heterogeneity of the inherent cell populations. Moreover, changes in cellular interconnections, membrane lipid and cholesterol compositions, compartment-specific biophysical properties, and intercellular space constituents demand technical adjustments [...] Read more.
Efficient purification of viable neural cells from the mature CNS has been historically challenging due to the heterogeneity of the inherent cell populations. Moreover, changes in cellular interconnections, membrane lipid and cholesterol compositions, compartment-specific biophysical properties, and intercellular space constituents demand technical adjustments for cell isolation at different stages of maturation and aging. Though such obstacles are addressed and partially overcome for embryonic premature and mature CNS tissues, procedural adaptations to an aged, progeroid, and degenerative CNS environment are underrepresented. Here, we describe a practical workflow for the acquisition and phenomapping of CNS neural cells at states of health, physiological and precocious aging, and genetically provoked neurodegeneration. Following recent, unprecedented evidence of post-mitotic cellular senescence (PoMiCS), the protocol appears suitable for such de novo characterization and phenotypic opposition to classical senescence. Technically, the protocol is rapid, efficient as for cellular yield and well preserves physiological cell proportions. It is suitable for a variety of downstream applications aiming at cell type-specific interrogations, including cell culture systems, Flow-FISH, flow cytometry/FACS, senescence studies, and retrieval of omic-scale DNA, RNA, and protein profiles. We expect suitability for transfer to other CNS targets and to a broad spectrum of engineered systems addressing aging, neurodegeneration, progeria, and senescence. Full article
(This article belongs to the Special Issue Cellular Senescence in Physiological and Pathological Processes)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop