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Immunosenescence in prostate cancer: from aging-related immune dysfunction to therapeutic opportunities.

Prostate cancer is a typical age-associated malignancy, and increasing evidence suggests that age-related immune alterations play an importa … ps in an immunologically "cold" and suppressive tumor milieu. In addition to systemic immune aging, cellular senescence and the senescence-associated secretory phenotype (SASP) further reshape the local microenvironment by promoting chronic inflammation, stromal remodeling, and immune dysfunction. Together, immunosenescence, inflammaging, and senescence-related signa …

WNT16 elevation induced cell senescence of osteoblasts in ankylosing spondylitis.

BACKGROUND: WNT16 is critical for bone homeostasis, but the effect of WNT16 in ankylosing spondylitis (AS) is still unknown. Here, we investigated whether WNT16 influences bone formation and pathophysiological changes of AS in an in vitro model. METHODS: The bone tissue from the facet joints was obtained from seven disease control and seven AS patients. Primary osteoprogenitor cells of the facet joints were isolated using an outgrowth method. Isolated osteoprogenitor cells from both control and AS tissues were analyzed by microarray, RT-qPCR, immunoblotting, and immunohistochemistry. The bone

Identification of microRNA-mRNA functional interactions in UVB-induced senescence of human diploid fibroblasts.

BACKGROUND: Cellular senescence can be induced by a variety of extrinsic stimuli, and sustained exposure to sunlight is a key factor in photoaging of the skin. Accordingly, irradiation of skin fibroblasts by UVB light triggers cellular senescence, which is thought to contribute to extrinsic skin aging, although molecular mechanisms are incompletely understood. Here, we addressed molecular mechanisms underlying UVB induced senescence of human diploid fibroblasts. RESULTS: We observed a parallel activation of the p53/p21(WAF1) and p16(INK4a)/pRb pathways. Using genome-wide transcriptome analysi…

Использование естественных экзоцитозных везикул для борьбы с возрастными заболеваниями: от возрастных драйверов до терапевтических возможностей.

Старение — это сложный биологический процесс, приводящий к увеличению нагрузки возрастных заболеваний (ARD). Клеточная старость, включающая необратимое остановку клеточного цикла и выделение фенотипа секреторной активности при старении (SASP), играет центральную роль в старении и развитии ARD. Естественные экзоцитические везикулы (NEVs) — это везикулы, полученные из клеток, органов и тканей без искусственных вмешательств. В последние годы NEVs привлекли внимание как медиаторы межклеточной коммуникации, и показали многофункциональный потенциал в регулировании клеточной старости и ARD. С одной с

Совпадение в аннотации оригинала
Aging is a complex biological process that leads to a growing burden of age-related diseases (ARD). Cellular senescence, which involves irreversible cell cycle arrest and the release of senescence-associated secretory phenotype (SASP), plays a central role in aging and the development of ARD. Natural extracellular vesicles (NEVs) refer to vesicles that deriv…

Identification of ribonucleotide reductase M2 as a potential target for pro-senescence therapy in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading cause of gynecological-related cancer deaths in the United States. There is, therefore, an urgent need to develop novel therapeutic strategies for this devastating disease. Cellular senescence is a state of stable cell growth arrest that acts as an important tumor suppression mechanism. Ribonucleotide reductase M2 (RRM2) plays a key role in regulating the senescence-associated cell growth arrest by controlling biogenesis of 2'-deoxyribonucleoside 5'-triphosphates (dNTPs). The role of RRM2 in EOC remains poorly understood. Here we show that RRM2 is…

Targeting Protein-Protein Interactions (PPIs) to Drive Functional Annotation: An Integrative Methodology to Study Senescence-Associated PPIs Using TMPRSS11a as Model Interactor.

Protein-protein interactions (PPIs) play a central role in regulating cellular processes. However, the identification and characterization of senescence-associated PPIs remain challenging. In this study, we developed and evaluated an integrative methodology based on selective proteomics to identify PPIs associated with cellular senescence induced by TMPRSS11a. We started from isolated proteins that co-immunoprecipitated with TMPRSS11a and were subsequently identified by mass spectrometry. Building on this dataset, we implemented a workflow combining selective proteomics, structural bioinformat…

Placentas From SARS-CoV-2 Infection During Pregnancy Exhibit Foci of Oxidative Stress and DNA Damage.

PROBLEM: COVID-19 during pregnancy is linked to increased maternal morbidity and a higher incidence of preterm births (PTBs), yet the underlying mechanisms remain unclear. Cellular senescence, characterized by the irreversible cessation of cell division, is a critical process in placental function, and its dysregulation has been implicated in pregnancy complications like PTB. Senescence can be induced by various stressors, including oxidative stress, DNA damage, and viral infections. METHOD OF STUDY: In this study, we determined whether COVID-19 had an impact on placental senescence. We exami…

Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis.

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early pass…

Senolytic therapy increases replicative capacity by eliminating senescent endothelial cells.

Aging is the greatest risk factor for cardiovascular diseases (CVD) and is characterized by inflammation, oxidative stress, and cellular senescence. Cellular senescence is a state of persistent cell cycle arrest triggered by stressors such as DNA damage and telomere attrition. Senescent endothelial cells (ECs) can impair vascular function and promote inflammation, thereby contributing to CVD progression. Senolytics, a class of drugs that selectively eliminate senescent cells, have been shown to remove senescent ECs, but their effects on the replicative capacity and genomic integrity of aged, e…

Participation of ATM, SMG1, and DDX5 in a DNA Damage-Induced Alternative Splicing Pathway.

Altered cellular responses to DNA damage can contribute to cancer development, progression, and therapeutic resistance. Mutations in key DNA … alternatively spliced to generate TP53b mRNA and p53b protein is required for optimal induction of cellular senescence after ionizing radiation-induced DNA damage. Herein, we confirmed and extended these observations by demonstrating that the ATM protein kinase is required for repression of SMG1 kinase activity after ionizing radiation. We found that the RNA helicas …

PP4 deficiency drives airway epithelial senescence via the PERK-eIF2α-ATF4-p21 axis in severe asthma.

BACKGROUND: Cellular senescence, defined by irreversible cell cycle arrest and the senescence-associated secretory phenotype (SASP), has emerged as a critical driver of airway inflammation and hyperresponsiveness in asthma. Despite well-established associations between senescence, aging, and chronic disease, its precise mechanistic role in asthma pathogenesis remains poorly understood. Protein phosphatase 4 (PP4), a serine/threonine phosphatase with broad physiological functions, is significantly downregulated in airway epithelial cells derived from patients with severe asthma, suggesting a po…

Acute Kidney Injury as a Condition of Renal Senescence.

Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is … se. During abnormal kidney repair, tubular epithelial cells can assume a senescence-like phenotype. Cellular senescence can occur as a result of cell cycle arrest due to increased expression of cyclin kinase inhibitors (mainly p21), downregulation of Klotho expression, and telomere shortening. In AKI, cellular senescence is aggravated by other factors including oxida …

SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters.

Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide (NMN) have been identified, but the cellular transporter of nicotinamide has not been elucidated. Here, we demonstrate that equilibrative nucleoside transporter 1 and 2 (ENT1 and 2, encoded by SLC29A1 and 2) drive cellular nicotinamide uptake and establish nicotinamide metabolism homeostasis. In addition, ENT1/2 exhibits a strong capacity to change the cellular

When defense turns dangerous: The dual nature of senescence in pancreatic ductal adenocarcinoma.

Cellular senescence has emerged as a context-dependent determinant of pancreatic ductal adenocarcinoma (PDAC) progression and therapeutic response. In early pancreatic tumorigenesis, oncogene-induced senescence acts as a robust tumor-suppressive mechanism that limits KRAS-driven malignant transformation. However, this protective barrier is progressively circumvented during disease evolution. In established PDAC, senescence acquires predominantly pro-tumorigenic functions, particularly within the stromal compartment. Senescent cancer-associated fibroblasts reshape the tumor microenvironment thr…

Mitochondrial fatty acid oxidation drives senescence.

Cellular senescence is a stress-induced irreversible cell cycle arrest involved in tumor suppression and aging. Many stresses, such as telomere shortening and oncogene activation, induce senescence by damaging nuclear DNA. However, the mechanisms linking DNA damage to senescence remain unclear. Here, we show that DNA damage response (DDR) signaling to mitochondria triggers senescence. A genome-wide small interfering RNA screen implicated the outer mitochondrial transmembrane protein BNIP3 in senescence induction. We found that BNIP3 is phosphorylated by the DDR kinase ataxia telangiectasia mut…

Senolytics cocktail dasatinib and quercetin alleviate chondrocyte senescence and facet joint osteoarthritis in mice.

BACKGROUND CONTEXT: Low back pain (LBP) is a pervasive issue, causing substantial economic burden and physical distress worldwide. Facet joi … lumbar facet joint (LFJ) samples were obtained to investigate the relationship between chondrocyte cellular senescence and LFJ osteoarthritis (OA). Subsequently, we established an in vitro model of excessive mechanical stress on chondrocytes and an in vivo bipedal standing mice model to induce LFJ OA. IHC (immunohistochemistry) staining in vivo and SA-β-gal staining …

NAD+ supplementation prevents STING-induced senescence in ataxia telangiectasia by improving mitophagy.

Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A-T). Loss of mitochondrial function can drive age-related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in A-T patient fibroblasts, and in ATM-deficient cells and mice. Senescence is mediated by stimulator of interferon genes (STING) and in…

Impact of Progerin Expression on Adipogenesis in Hutchinson-Gilford Progeria Skin-Derived Precursor Cells.

Hutchinson-Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the loss of general subcutaneous fat. To determine whether premature cellular senescence is responsible for the altered adipogenesis in patients with HGPS, we evaluated the differentiation of HGPS skin-derived precursor stem cells (SKPs) into adipocytes. The SKPs were isolated from primary human HGPS…

The ageing microenvironment in sarcopenia: early alterations and targeted therapeutic strategies.

Sarcopenia is a progressive skeletal muscle disorder associated with ageing and characterized by declines in muscle strength, mass and function. Increasing evidence suggests that its development is not driven solely by myofiber atrophy or impaired protein metabolism, but also by early remodeling of the ageing skeletal muscle microenvironment. This Review summarizes key early alterations in sarcopenia, including dysregulated immune homeostasis, cellular senescence and the senescence-associated secretory phenotype, depletion and dysfunction of muscle satellite cells, disruption of the regenerati…

The senomorphic impact of astaxanthin on irradiated rat spleen: STING, TLR4 and mTOR contributed pathway.

OBJECTIVES: Exposure of spleen tissues to ionizing radiation during radiotherapy can induce cellular stress and immune-dysfunction leading to cellular senescence. INTRODUCTION: The process of a cancerous development is facilitated by the accumulation of senescent cells. This justifies the incorporation of anti-senescent medications during splenic irradiation (SI). METHODS: In this study senescence was induced in the spleen of male albino rats by radiation exposure (5Gy-single whole body gamma-irradiation) then after 2 weeks, oral astaxanthin regimen was started once daily in a dose of 25 mg/…