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Inactivation of AKT induces cellular senescence in uterine leiomyoma.

Uterine leiomyomas (fibroids) are a major public health problem. Current medical treatments with GnRH analogs do not provide long-term benefit. Thus, permanent shrinkage or inhibition of fibroid growth via medical means remains a challenge. The AKT pathway is a major growth and survival pathway for fibroids. We propose that AKT inhibition results in a transient regulation of specific mechanisms that ultimately drive cells into cellular senescence or cell death. In this study, we investigated specific mechanisms of AKT inhibition that resulted in senescence. We observed that administration of M…

Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence.

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in the United States. Thus, there is an urgent need to develop novel therapeutics for this disease. Cellular senescence is an important tumor suppression mechanism that has recently been suggested as a novel mechanism to target for developing cancer therapeutics. Wnt5a is a noncanonical Wnt ligand that plays a context-dependent role in human cancers. Here, we investigate the role of Wnt5a in regulating senescence of EOC cells. We show that Wnt5a is expressed at significantly lower levels in human EOC cell lines and …

Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts.

Magnesium inadequacy affects more than half of the U.S. population and is associated with increased risk for many age-related diseases, yet … -term consequence of inadequate magnesium availability in human fibroblast cultures was accelerated cellular senescence, which may be a mechanism through which chronic magnesium inadequacy could promote or exacerbate age-related disease.

Targeting cellular senescence in dermatology: senolytic and senomorphic strategies.

Cellular senescence has emerged as a central mechanism driving cutaneous aging, impaired regeneration, and numerous dermatologic pathologies. Initially evolved as a protective mechanism to prevent malignant transformation and facilitate wound repair, senescence becomes maladaptive when senescent cells persist. Senescent keratinocytes, fibroblasts, and melanocytes can secrete pro-inflammatory mediators and other factors, collectively termed the senescence-associated secretory phenotype (SASP), which may degrade extracellular matrix components, disrupt pigmentary balance, and impair barrier func…

Formononetin attenuates cellular senescence through a FOS-mediated mechanism.

Cellular senescence is characterized by cell cycle arrest accompanied by mitochondrial dysfunction. Despite extensive efforts to overcome this stable state of growth arrest, effective strategies for treating cellular senescence have not been identified. In this study, we screened plant-derived secondary metabolites and confirmed that formononetin is a substance that potently induces the proliferation of senescent fibroblasts. Formononetin-induced proliferation was associated with the suppression of expression of key cell cycle inhibitors, including p53 and Rb-1. This proliferative response was…

Cellular Senescence in Human Periodontal Tissue: A Narrative Review.

OBJECTIVE(S): To evaluate naturally occurring cellular senescence in human gingival and periodontal ligament (PDL) tissues by addressing two questions: (1) whether susceptibility to cellular senescence increases with chronological aging, and (2) whether periodontitis lesions exhibit senescence-associated features indicative of inflammation-accelerated senescence. MATERIALS AND METHODS: A structured search of PubMed and bioRxiv databases identified 186 articles. After applying the inclusion criteria, 13 studies that investigated senescence markers in gingival and PDL tissues in the context of …

Clinical Features of Cellular Senescence Pathways in Severe Asthma.

BACKGROUND: Asthma severity increases with age, suggesting a role for accelerated biological ageing. We hypothesised that cellular senescence pathways such as the senescence-associated secretory pathway (SASP) and the p53-cellular senescence pathway are enriched in the airways of patients with severe asthma. METHODS: We utilised transcriptomic data from the U-BIOPRED cohort to analyse enrichment scores (ES) of p53 and SASP pathways in different airway compartments using gene set variation analysis. Findings in bronchial biopsies were validated in the independent NOVA cohort. We examined assoc…

Cellular senescence defining the disease characteristics of Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a complex and heterogeneous inflammatory disease whose most important feature is immune dysregulation. As a basic cell response, cellular senescence (CS) can regulate the immune response involved in a variety of inflammatory diseases. However, the role of CS in the pathogenesis and diagnosis prediction of CD are still unknown. METHODS: We utilized CD-related datasets from the GEO database for differential gene expression analysis, and CS related differentially expressed genes (CSRDEGs) in CD by a comprehensive bioinformatics analysis encompassing GSEA, WGCN…

Biomarkers of Cellular Senescence in Type 2 Diabetes Mellitus.

Although animal studies have linked cellular senescence to the pathogenesis and complications of type 2 diabetes mellitus (T2DM), there is a paucity of corroborating data in humans. Thus, we measured a previously validated marker for senescent cell burden in humans, T-cell expression of p16 mRNA, along with additional biomarkers, to compare the senescence phenotypes of postmenopausal control (lean, N = 37) and T2DM (N = 27) participants. To control for effects of obesity alone, we included a third group of obese but non-diabetic women (N = 29) who were matched for body mass index to the T2DM p…

Targeting Cellular Senescence: Pathophysiology in Multisystem Age-Related Diseases.

With the intensification of global aging, the incidence of age-related diseases (including cardiovascular, neurodegenerative, and musculoskeletal disorders) has been on the rise, and cellular senescence is identified as the core driving mechanism. Cellular senescence is characterized by irreversible cell cycle arrest, which is caused by telomere shortening, imbalance in DNA damage repair, and mitochondrial dysfunction, accompanied by the activation of the senescence-associated secretory phenotype (SASP). In this situation, proinflammatory factors and matrix-degrading enzymes can be released, t…

Новая граница для эпилепсического лечения, нацелившись на клеточную сенсацию.

Эпилепсия представляет собой опасное для жизни расстройство мозга, которое затрагивает около 1-2% населения мира. Были выявлены различные механизмы, способствующие развитию эпилепсии и распространению припадков. Тем не менее более глубокое понимание клеточных механизмов, лежащих в основе развития эпилепсии, необходимо для разработки более эффективных терапевтических стратегий лечения эпилепсии. Клеточная сенесцензия, клеточный механизм, в рамках которого развитие клеток постоянно прекращается и вызывает выход клеток из пролиферативного бассейна, связана с такими неврологическими расстройствами

Совпадение в аннотации оригинала
Epilepsy is a life-threatening brain disorder that affects about 1-2 % of the world's population. Various mechanisms facilitating epilepsy d … ilepsy development is necessary for designing better therapeutic strategies for epilepsy treatment. Cellular senescence, a cellular mechanism wherein cell growth is permanently halted and causes cells to exit the proliferative pool, has been associated with neurological disorders such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and epilepsy. How …

Stress Hormones: Unveiling the Role in Accelerated Cellular Senescence.

Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen sp…

SIRT-associated attenuation of cellular senescence in vascular wall.

This review focuses on the vital function that SIRT1 and other sirtuins play in promoting cellular senescence in vascular smooth muscle cells, which is a key element in the pathogenesis of vascular aging and associated cardiovascular diseases. Vascular aging is a gradual process caused by the accumulation of senescent cells, which results in increased vascular remodeling, stiffness, and diminished angiogenic ability. Such physiological alterations are characterized by a complex interplay of environmental and genetic variables, including oxidative stress and telomere attrition, which affect gen…

Mapping cellular senescence networks in human diabetic foot ulcers.

Cellular senescence, a cell fate defined by irreversible cell cycle arrest, has been observed to contribute to chronic age-related conditions including non-healing wounds, such as diabetic foot ulcers. However, the role of cellular senescence in the pathogenesis of diabetic foot ulcers remains unclear. To examine the contribution of senescent phenotypes to these chronic wounds, differential gene and network analyses were performed on publicly available bulk RNA sequencing of whole skin biopsies of wound edge diabetic foot ulcers and uninvolved diabetic foot skin. Wald tests with Benjamini-Hoch…

New insight into dyslipidemia-induced cellular senescence in atherosclerosis.

Atherosclerosis, characterized by lipid-rich plaques in the arterial wall, is an age-related disorder and a leading cause of mortality worldwide. However, the specific mechanisms remain complex. Recently, emerging evidence has demonstrated that senescence of various types of cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, endothelial progenitor cells (EPCs), and adipose-derived mesenchymal stem cells (AMSCs) contributes to atherosclerosis. Cellular senescence and atherosclerosis share various causative stimuli, in which dyslipidemia has attracted much…

Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives.

Mild traumatic brain injury (mTBI) can lead to long-term neurological dysfunction and increase one's risk of neurodegenerative disease. Several repercussions of mTBI have been identified and well-studied, including neuroinflammation, gliosis, microgliosis, excitotoxicity, and proteinopathy - however the pathophysiological mechanisms activating these pathways after mTBI remains controversial and unclear. Emerging research suggests DNA damage-induced cellular senescence as a possible driver of mTBI-related sequalae. Cellular senescence is a state of chronic cell-cycle arrest and inflammation ass…

Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis.

Cellular senescence entails a stable cell-cycle arrest and a pro-inflammatory secretory phenotype, which contributes to aging and age-related diseases. Obesity is associated with increased senescent cell burden and neuropsychiatric disorders, including anxiety and depression. To investigate the role of senescence in obesity-related neuropsychiatric dysfunction, we used the INK-ATTAC mouse model, from which p16Ink4a-expressing senescent cells can be eliminated, and senolytic drugs dasatinib and quercetin. We found that obesity results in the accumulation of senescent glial cells in proximity to…

PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis.

Cigarette smoke (CS)-induced accumulation of mitochondrial damage has been widely implicated in chronic obstructive pulmonary disease (COPD) … illuminate how PINK1 and PRKN regulate mitophagy in relation to CS-induced mitochondrial damage and cellular senescence, overexpression and knockdown experiments were performed in airway epithelial cells (AEC). In comparison to wild-type mice, prkn KO mice demonstrated enhanced airway wall thickening with emphysematous changes following CS exposure. AEC in CS-exposed …

Cellular senescence in ageing, age-related disease and longevity.

Cellular senescence is the state of permanent inhibition of cell proliferation. Senescent cells are characterized by several features including increased activity of senescence-associated β-galactosidase (SA-β-GAL) and senescenceassociated secretory phenotype (SASP). In vitro, 2 types of senescence have been described. One is telomere-dependent replicative senescence and the second is stress-induced premature senescence (SIPS). Despite some tissue-specific characteristics many kinds of cells, including stem/progenitor cells, can undergo senescence both in vitro and in vivo. Senescent cells wer…

Suppressing Dicer inhibits proliferation and contributes to cellular senescence, partially via a p21-associated senescence pathway.

Dicer is known to engage in regulating micro (mi)RNA biosynthesis. However, the role in driving thyroid carcinogenesis is unknown. In this study, we explored the role of Dicer in the carcinogenesis of well-differentiated thyroid carcinoma (WDTC). Thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure Dicer messenger (m)RNA and protein levels. Additionally, research into silencing Dicer1 in papillary thyroid cancer (PTC) (TPC-1), follicular thyroid cancer (FTC), and normal thyroid (Nthy-ori 3-1) cell lines was also applied to evaluate its effects on tumour behaviors. Di