Senescent Cells as Drivers of Age-Related Diseases
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Cellular senescence is a process of establishing a permanent growth arrest in cells, induced by a myriad of factors. It is proposed to contribute to the pathogenesis of many age-related disorders. Because of the implications of senescent cells in several diseases, it is suggested that these cells be eliminated in the body to improve and prolong healthspan in humans. Extensive research is being conducted to dampen the negative effects of senescence in humans. Although much progress has been made to understand the role of cellular senescence in several age-related diseases, there is still a lot of work to be done to produce clinically relevant drugs that will target senescent cells. It will take some time before senolytic drugs will be made available in the market. Nonetheless, it is with high hopes that we expect there will be major breakthroughs in the treatment of age-related pathologies in the coming decades.
Comparison of Healing Effect of DMSP in Green Sea Algae and Mesenchymal Stem Cells on Various Inflammatory Disorders
Se-Kwon Kim in Marine Biochemistry, 2023
Whereas the pace of population aging around the world is increasing dramatically (WHO, 2015). Aging is the fundamental and unavoidable factor for the development of cancer. The incidence of cancer rises dramatically with age, most likely due to a build-up of risks for specific cancers that increase with age. The overall risk accumulation is combined with the tendency for cellular repair mechanisms to be less effective as a person grows older. Therefore, cancers have been the most tragic and terrible disorders for humans. In the cells of tissues and organs, the cellular senescence is exposed to nonlethal intrinsic or extrinsic stress that results in persistent growth arrest with a distinct morphological and biochemical phenotype. The engagement of senescence may represent a key component for therapeutic intervention in the eradication of cancer occurring with ageing. Normal cells in the body follow an orderly path of growth, division, and death. When this process breaks down, cancer begins to form. Unlikely, regular cells, cancer cells do not experience programmatic death and instead continue to grow and divide. This leads to a mass of abnormal cells that grow out of control. Accordingly, the cellular senescence in anti-cancer therapy may be important also in aging because of the age related-changes down-regulation at the level of both cancer suppressor genes and immune functions (Provinciali et al., 2013; Fulop et al., 2013; Tollefsbol, 2014). This indicates that people age 65 and older bear a higher risk of suffering from cancer compared to younger people (Misra, Seo & Cohen, 2004; WHO, 2018).
Mitochondrial Stress and Cellular Senescence
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
Other than mitochondrial stress, a myriad of stimuli can also induce cellular senescence, including telomere shortening, DNA damage, chromatin perturbations, tumor suppressor activation, oncogenic stimulation, cytotoxic chemical exposure, and oxidative stress (Campisi 2013; Hernandez-Segura, Nehme, and Demaria 2018; Loaiza and Demaria 2016; Marquez and Velarde 2017). Replicative senescence (RS) occurs in cells with dysfunctional telomeres (Victorelli and Passos 2017). Stress-induced senescence (SIS) is caused by stressors or mechanisms other than telomere shortening (DeMagalhães and Passos 2018; Herbig et al. 2004; Ramirez et al. 2001). This may include DNA-damaging agents (e.g., UV, ionizing radiation), chemotherapeutic drugs, and oxidative stress (Hernandez-Segura, Nehme, and Demaria 2018; Toussaint, Medrano, and von Zglinicki 2000). Oncogene-induced senescence (OIS) results from the hyperactivation of mitogenic oncogenes or the inactivation of tumor suppressor genes (Campisi and d’Adda Di Fagagna 2007; Gorgoulis and Halazonetis 2010). Mitogenic oncogenes include RAS (Serrano et al. 1997), RAF (Zhu et al. 1998), MEK (Lin et al. 1998) and BRAF (Michaloglou et al. 2005). Paracrine senescence (PS) occurs when molecules secreted by a primary senescent cell induces senescence in a surrounding non-senescent cell (Acosta et al. 2013). This is also referred to as “bystander senescence” (Hubackova et al. 2012) or senescence-induced senescence (Nelson et al. 2012).
The Effect of Resveratrol on Cellular Senescence in Normal and Cancer Cells: Focusing on Cancer and Age-Related Diseases
Published in Nutrition and Cancer, 2019
Hossein Farhadnejad, Hadi Emamat, Hamid Zand
Cellular senescence refers to the essentially irreversible arrest of cell proliferation or growth, which is leading to important changes in cell phenotype, including permanent arrest of cell proliferation, development of resistance to apoptosis in some cell types, and changes in the patterns of gene expression (1, 2). This process occurs when cells experience potentially oncogenic stimuli, including persistent telomeric or genomic damage, oncogenes, strong mitogenic signals, epigenomic damages, and tumor suppressor gene activation (1, 3). The consequences of cellular senescence are different across various senescent cell phenotypes. It has been suggested that cellular senescence can have both adverse and beneficial effects based on the physiological context. Induction of inflammation and damage to normal tissue structure as well as function are among the detrimental effects of cellular senescence. In contrast, promoting tumor suppression, inducing immune clearance of senescent cells, and optimal repair of damaged are major beneficial consequences of this process (2, 4–6).
Cellular senescence in liver fibrosis: Implications for age-related chronic liver diseases
Published in Expert Opinion on Therapeutic Targets, 2021
Wanvisa Udomsinprasert, Abhasnee Sobhonslidsuk, Jiraphun Jittikoon, Sittisak Honsawek, Usa Chaikledkaew
From the studies described above, it is conceivable that an increased understanding of the senescence program relevant to liver fibrosis would expand the clinical spectrum of therapeutic opportunities for the treatment of liver fibrosis. In general, cellular senescence can be triggered by several stressors including telomere dysfunction, oxidative stress, and non-telomeric DNA damage and is also characterized by cell-cycle arrest, resistance to apoptosis, and epigenetic changes including the formation of senescence-associated heterochromatic foci and the senescence-associated secretory phenotype. We discuss below the evidence for causes of cellular senescence relevant to liver fibrosis, including telomere attrition and mitochondria dysfunction in the context of a plethora of chronic liver diseases.
Genistein alleviates H2O2-induced senescence of human umbilical vein endothelial cells via regulating the TXNIP/NLRP3 axis
Published in Pharmaceutical Biology, 2021
Guihua Wu, Siming Li, Guangjin Qu, Jiajia Hua, Jing Zong, Xiaofeng Li, Fanghui Xu
Senescence is an irreversible form of long-term cell-cycle arrest, caused by excessive intracellular or extracellular stress or damage (Noren Hooten and Evans 2017; Dodig et al. 2019), and cellular senescence refers to the arrest in the G1 phase of the cell-cycle (Vicencio et al. 2008). In addition, cellular senescence has been reported to be a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation (Chinta et al. 2015). Researchers have identified many stressors that are able to induce senescence, such as H2O2 (Song et al. 2014). Li et al. (2016) proposed that H2O2 treatment significantly inhibited the migration and proliferation of HUVECs in a dose-dependent manner. In our study, in order to establish a primary cell-induced disease model that was more clinically and physiologically relevant to human disease, H2O2-treated HUVECs were employed to discover the possible small molecules or the underlying mechanism for improving H2O2-induced senescence of HUVECs. Besides, it was noted that H2O2 inhibited the proliferation and cell cycle G1/S transition and promoted the senescence of HUVECs.
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