Результаты поиска

Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease.

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an … rch efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction including energy starvation and oxidative stress, mitochondria dynamics imbalance, cell a …

Cellular senescence contributes to spontaneous repair of the rat meniscus.

Cellular senescence, traditionally associated with aging and chronic diseases, has recently been identified as a potential facilitator of tissue regeneration via a senescence-associated secretory phenotype (SASP). In rodents, the meniscus is known to regenerate spontaneously from the surrounding synovium, but the mechanism, and especially its relationship to cellular senescence, remains unclear. This study investigated the contribution of cellular senescence to spontaneous repair of the rat meniscus. We created a rat partial medial meniscectomy (pMx) model to evaluate time-course changes in re…

Cellular senescence in hepatocytes contributes to metabolic disturbances in NASH.

Cellular senescence is a state of irreversible cell cycle arrest and has been shown to play a key role in many diseases, including metabolic diseases. To investigate the potential contribution of hepatocyte cellular senescence to the metabolic derangements associated with non-alcoholic steatohepatitis (NASH), we treated human hepatocyte cell lines HepG2 and IHH with the senescence-inducing drugs nutlin-3a, doxorubicin and etoposide. The senescence-associated markers p16, p21, p53 and beta galactosidase were induced upon drug treatment, and this was associated with increased lipid storage, incr…

Cellular senescence and cardiovascular diseases: moving to the "heart" of the problem.

Cardiovascular diseases (CVDs) constitute the prime cause of global mortality, with an immense impact on patient quality of life and disability. Clinical evidence has revealed a strong connection between cellular senescence and worse cardiac outcomes in the majority of CVDs concerning both ischemic and nonischemic cardiomyopathies. Cellular senescence is characterized by cell cycle arrest accompanied by alterations in several metabolic pathways, resulting in morphological and functional changes. Metabolic rewiring of senescent cells results in marked paracrine activity, through a unique secret…

Effects of Air Pollution on Cellular Senescence and Skin Aging.

The human skin is exposed daily to different environmental factors such as air pollutants and ultraviolet (UV) light. Air pollution is considered a harmful environmental risk to human skin and is known to promote aging and inflammation of this tissue, leading to the onset of skin disorders and to the appearance of wrinkles and pigmentation issues. Besides this, components of air pollution can interact synergistically with ultraviolet light and increase the impact of damage to the skin. However, little is known about the modulation of air pollution on cellular senescence in skin cells and how t…

Cellular Senescence and the Kidney: Potential Therapeutic Targets and Tools.

Chronic kidney disease (CKD) is an increasing health burden (affecting approximately 13.4% of the population). Currently, no curative treatment options are available and treatment is focused on limiting the disease progression. The accumulation of senescent cells has been implicated in the development of kidney fibrosis by limiting tissue rejuvenation and through the secretion of pro-fibrotic and pro-inflammatory mediators termed as the senescence-associated secretory phenotype. The clearance of senescent cells in aging models results in improved kidney function, which shows promise for the op

Совпадение в полном тексте источника
… The latter situation/condition is also known as cellular senescence ( Campisi and d’Adda di Fagagna, 2007 ). … An expert review on the apoptotic balance in cellular senescence is provided by Childs et al. (2014) . …

Tau protein aggregation is associated with cellular senescence in the brain.

Tau protein accumulation is the most common pathology among degenerative brain diseases, including Alzheimer's disease (AD), progressive sup … ning neurons microdissected from postmortem AD brain revealed an expression profile consistent with cellular senescence. This complex stress response induces aberrant cell cycle activity, adaptations to maintain survival, cellular remodeling, and metabolic dysfunction. Using four AD transgenic mouse models, we found that NFTs, but not Aβ plaques, display a senescence …

[Cellular senescence as a common denominator in age-related diseases].

Cellular senescence has been traditionally characterized by cell cycle arrest of pot-mitotic cells as a response to a cellular damage. Now is known that senescent cells secret a diverse array of cytokines, chemokines, growth factors and other that altogether are called senescence associates secretory phenotype (SASP), which might have beneficial or deleterious effects on neighbor cells. This review describes those effects as well as the relationship between the SASP and several age related diseases. We also analyze the direction that recent investigations are turning in order to modulate or av…

The Bidirectional Role of Cellular Senescence in the Treatment of Ovarian Cancer.

Cellular senescence plays a complex and crucial dual role in ovarian cancer treatment: it serves as both an important tumor suppression mechanism and a potential driver of drug resistance and recurrence. This review systematically examines the intricate regulatory network of cellular senescence, encompassing multiple pathways including telomere dysfunction, DNA damage response, epigenetic remodeling, hormone signaling, and metabolic reprogramming. Studies have demonstrated that core therapeutic modalities, such as platinum-based chemotherapy, PARP inhibitors, and CDK4/6 inhibitors, can exert a…

The role of cellular senescence in wound healing of diabetic skin.

Diabetic foot ulcers are a severe complication of diabetes mellitus, characterized by impaired wound healing due to complex pathophysiological mechanisms. Cellular senescence, particularly the senescence-associated secretory phenotype (SASP), contributes to delayed healing by inducing persistent inflammation and dysfunction in dermal fibroblasts, macrophages and adipose tissue cells. Here, we review the molecular pathways leading to senescence in these cell types, including p53/p21 activation and apoptosis resistance, and how their SASP perpetuates chronic inflammation and impairs tissue regen…

New insights into the role of cellular senescence and rheumatic diseases.

Rheumatic disease is a chronic inflammatory disease that imposes significant societal and economic burdens. Accumulating evidence has demonstrated that cellular senescence plays an important role in inflammation-induced rheumatic diseases. Due to the lack of effective therapies, there is an urgent need for a deeper understanding of the etiopathogenesis of rheumatic diseases. In this review, we systematically summarized the role of cellular senescence in rheumatic diseases. We first focused on the mechanisms and hallmarks of cellular senescence, and then summarized evidence that can induce or a…

New insights into the role of cellular senescence and chronic wounds.

Chronic or non-healing wounds, such as diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), pressure ulcers (PUs) and wounds in the elderly etc., impose significant biological, social, and financial burdens on patients and their families. Despite ongoing efforts, effective treatments for these wounds remain elusive, costing the United States over US$25 billion annually. The wound healing process is notably slower in the elderly, partly due to cellular senescence, which plays a complex role in wound repair. High glucose levels, reactive oxygen species, and persistent inflammation are key fact…

Targeting cellular senescence as a therapeutic vulnerability in gastric cancer.

AIMS: Cellular senescence (CS) represents an intracellular defense mechanism responding to stress signals and can be leveraged as a "vulnerability" in cancer treatment. This study aims to construct a CS atlas for gastric cancer (GC) and uncover potential therapeutics for GC patients. MATERIALS AND METHODS: 38 senescence-associated regulators with prognostic significance in GC were obtained from the CellAge database to construct Gastric cancer-specific Senescence Score (GSS). Using eXtreme Sum algorism, GSS-based drug repositioning was conducted to identify drugs that could antagonize GSS in C…

Cellular senescence in recurrent tonsillitis and tonsillar hypertrophy in children.

OBJECTIVE: To observe the difference in cellular senescence patterns between recurrent tonsillitis and tonsillar hypertrophy. METHODS AND MATERIALS: Forty-three patients diagnosed with recurrent tonsillitis or tonsillar hypertrophy, based on medical history and symptoms, underwent tonsillectomy. The specimens were collected and examined using senescence β-galactosidase staining for cellular senescence. Macrophages were detected by immunochemistry. RESULTS: Cellular senescence was found in both recurrent tonsillitis and tonsillar hypertrophy groups. The comparison of cellular senescence in mi…

Angiotensin inhibition and cellular senescence in the developing rat kidney.

Cellular senescence is important for the maintenance of tissue homeostasis during normal development. In this study, we aimed to investigate the effect of renin angiotensin system (RAS) blockade on renal cell senescence in the developing rat kidney. Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle for seven days after birth. We investigated the intrarenal expressions of cell cycle regulators p21 and p16 with immunoblots and immunohistochemistry at postnatal day 8. For the determination of renal cellular senescence, immunostaining for senescence-associated β-galactosidase …

Cellular dehydration and immunoglobulin binding in senescent neonatal erythrocytes.

The life span of neonatal erythrocytes (60-80 days) is shorter than that of adult erythrocytes (120 days). We studied neonatal red blood cells separated on stractan density gradients to further characterize the aging process and to explore the possibility that senescence antigens play a role in the destruction of neonatal erythrocytes. Quantitation of membrane proteins 4.1a and 4.1b served as a marker for cell age and confirmed an enrichment for senescent red cells in the most dense layers of the gradients. Despite the shorter life span of neonatal erythrocytes, cord blood contained a larger p

The Senescence Associated Secretory Phenotype, a key marker of cellular senescence, is elevated in depression and moderated by sex.

OBJECTIVE: Studies have found elevation in a key biomarker of aging (the senescence-associated secretory phenotype (SASP) index) in depression. We investigated whether sex moderates the association between the SASP and major depression in older adults. METHODS: We included 423 older adults in a current major depressive episode and 140 adults with no history of depression. We measured the plasma levels of SASP biomarkers using multiplex immunoassays. The interaction effect between sex, depression diagnosis, and senescence markers were analyzed by general linear models, adjusted for confounding

LARS regulates cellular senescence and autophagy in liver cancer cells.

Human cytoplasmic leucyl-tRNA synthetase (LARS) is known to catalyze the ligation of leucine to tRNALeu during protein biosynthesis. However … g, differentially expressed genes in response to LARS knockdown were significantly clustered in the cellular senescence pathway. Elevated p21 and p16 expression with increased senescence-associated β-galactosidase activity was observed in LARS knockdown HepG2 cells. In addition, autophagy with increasing autophagic flux was triggered in LARS knockdown HepG2 cells. Fu …

Cellular senescence: the "hidden driver" in chronic inflammatory skin disorders.

Chronic inflammatory skin disorders are characterized by persistent skin inflammation, impaired barrier function, and frequent recurrence, all of which substantially reduce patients' quality of life. Traditional studies attribute the pathogenesis of these diseases to immune dysregulation, whereas new evidence indicates that cellular senescence is a key risk factor and a mechanism underlying disease progression. Cellular senescence, defined by irreversible cell cycle arrest, is accompanied by a senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and DNA damage. This rev…

Cellular senescence dysregulates antiviral interferon responses in idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are highly vulnerable to respiratory virus infections, but the cellular mechanisms linking fibrotic remodeling to impaired local antiviral defense remain unclear. Here, we investigated how cellular senescence shapes the response of patient-derived healthy and IPF primary lung fibroblasts to influenza A virus (IAV) infection. Transcriptomic profiling identified infection as the driver of gene expression in both DNA damage-induced senescent healthy and IPF fibroblasts and revealed induction of canonical antiviral pathways in both cell states. How…