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      Immunosenescence and Skin: A State of Art of Its Etiopathogenetic Role and Crucial Watershed for Systemic Implications

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      International Journal of Molecular Sciences
      MDPI AG

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          Abstract

          Immunosenescence is a complex multifactorial phenomenon consisting of wide-ranging remodeling of the immune system during the life span, resulting in an age-related qualitative–quantitative decline of immune cells and cytokines. A growing body of evidence in the international literature is highlighting the etiopathogenetic role of skin immunosenescence in the onset of various dermatologic conditions. Skin immunosenescence also serves as an interesting watershed for the onset of system-wide conditions in the context of allergic inflammation. Moreover, in recent years, an increasingly emerging and fascinating etiopathogenetic parallelism has been observed between some mechanisms of immunosenescence, both at cutaneous and systemic sites. This would help to explain the occurrence of apparently unconnected comorbidities. Throughout our review, we aim to shed light on emerging immunosenescent mechanisms shared between dermatologic disorders and other organ-specific diseases in the context of a more extensive discussion on the etiopathogenetic role of skin immunosenescence. A promising future perspective would be to focus on better understanding the mutual influence between skin and host immunity, as well as the influence of high inter-individual variability on immunosenescence/inflammaging. This can lead to a more comprehensive “immunobiographic” definition of each individual.

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

            Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stimuli, as well as developmental signals. Senescence is considered to be a highly dynamic, multi-step process, during which the properties of senescent cells continuously evolve and diversify in a context dependent manner. It is associated with multiple cellular and molecular changes and distinct phenotypic alterations, including a stable proliferation arrest unresponsive to mitogenic stimuli. Senescent cells remain viable, have alterations in metabolic activity and undergo dramatic changes in gene expression and develop a complex senescence-associated secretory phenotype. Cellular senescence can compromise tissue repair and regeneration, thereby contributing toward aging. Removal of senescent cells can attenuate age-related tissue dysfunction and extend health span. Senescence can also act as a potent anti-tumor mechanism, by preventing proliferation of potentially cancerous cells. It is a cellular program which acts as a double-edged sword, with both beneficial and detrimental effects on the health of the organism, and considered to be an example of evolutionary antagonistic pleiotropy. Activation of the p53/p21WAF1/CIP1 and p16INK4A/pRB tumor suppressor pathways play a central role in regulating senescence. Several other pathways have recently been implicated in mediating senescence and the senescent phenotype. Herein we review the molecular mechanisms that underlie cellular senescence and the senescence associated growth arrest with a particular focus on why cells stop dividing, the stability of the growth arrest, the hypersecretory phenotype and how the different pathways are all integrated.
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              Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis

              The prognostic value of FoxP3+ regulatory T cells (Tregs) in cancer remains controversial. We did a meta-analysis to assess the prognostic effect of FoxP3+ Treg across different types of cancer and to investigate factors associated with variations in this effect. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched to identify eligible studies. In total, we analyzed 76 articles encompassing 17 types of cancer, and including 15,512 cancer cases. The overall pooled analysis including all types of cancer suggested FoxP3+Tregs had a significant negative effect on overall survival (OS) (OR 1.46, P < 0.001), but the prognostic effect varied greatly according to tumor site. High FoxP3+ Tregs infiltration was significantly associated with shorter OS in the majority of solid tumors studied, including cervical, renal, melanomas, and breast cancers, et al; whereas, FoxP3+ Tregs were associated with improved survival in colorectal, head and neck, and oesophageal cancers. The stratified analysis suggested the molecular subtype and tumor stage significantly influenced the prognostic value of FoxP3+ Tregs in certain types of cancer. In conclusion, our meta-analysis suggests that the prognostic role of FoxP3+ Tregs was highly influenced by tumor site, and was also correlated with the molecular subtype and tumor stage.
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                Author and article information

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                Journal
                IJMCFK
                International Journal of Molecular Sciences
                IJMS
                MDPI AG
                1422-0067
                May 2023
                April 27 2023
                : 24
                : 9
                : 7956
                Article
                10.3390/ijms24097956
                37175661
                1226d7ad-e26e-4973-924e-f3065e892f26
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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