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Aqueous Extract of Buddleja globosa Modulates Oxidative Stress-Induced Senescence-Associated Responses in THP-1-Derived Macrophages.

Background/Objectives: Cellular senescence and oxidative stress contribute to macrophage dysfunction and chronic inflammation during aging. Buddleja globosa (matico) is traditionally consumed as an infusion and has reported antioxidant and anti-inflammatory properties. This study evaluated whether an aqueous extract of B. globosa (BgAE) modulates senescence-associated responses in THP-1-derived macrophages exposed to hydrogen peroxide. Methods: The phenolic profile of BgAE was analyzed by HPLC-DAD and its antioxidant capacity by the oxygen radical absorbance capacity assay. Cell viability was …

Nrg1/ErbB signaling-mediated regulation of fibrosis after myocardial infarction.

Appropriate fibrotic tissue formation after myocardial infarction (MI) is crucial to the maintenance of the heart's structure. M2-like macrophages play a vital role in post-MI fibrosis by activating cardiac fibroblasts. Because the mechanism by which post-MI cardiac fibrosis is regulated is not fully understood, we investigated, in vitro and in vivo, the cellular and molecular mechanisms of post-MI fibrotic tissue formation, especially those related to the regulation of cellular senescence and apoptosis. CD206+ F4/80+ CD11b+ M2-like macrophages collected from mouse hearts on post-MI day 7 show…

Cinnamon polysaccharides reshape gut microbiota and enrich Alloprevotella rava to promote acetate-dependent choline metabolism and delay mammary aging.

BACKGROUND: Aging disrupts choline metabolism, impairs mitochondrial function, and accelerates tissue degeneration. As gut microbes critically influence host nutrient handling, microbiota-targeted interventions may provide a promising strategy to delay mammary senescence. PURPOSE: This study aimed to determine whether cinnamon polysaccharides (CP) and the commensal bacterium, Alloprevotella rava, could remodel host gut microbiota, enhance host choline utilisation, improve mitochondrial function, and thereby delay mammary senescence. STUDY DESIGN: An experimental study was conducted using mou

Downregulation of ALKBH5 rejuvenates aged human mesenchymal stem cells and enhances their therapeutic efficacy in myocardial infarction.

Despite promising results in myocardial infarction (MI), mesenchymal stem cell (MSC)-based therapy is limited by cell senescence. N6-methyla … d CDKN1C expression, leading to MSC senescence. CDKN1C overexpression ameliorated the inhibition of cellular senescence of ALKBH5 siRNA-treated AMSCs. More importantly, compared with AMSCs, shALKBH5-AMSCs transplantation provided a superior cardioprotective effect against MI in mice by improving MSC survival and angiogenesis. We determined that ALKBH5 accelerated MSC …

Proteomic revelations.

The power of proteomics in cultured skin fibroblasts from individuals with either systemic sclerosis or recessive dystrophic epidermolysis bullosa has led to the common finding of senescence and deficiencies in autophagy. Both of these disorders exert high demand on fibroblast activity, and without the protective action of autophagy cellular stress could have many adverse effects that are further amplified by the senescent phenotype.

Low-intensity pulsed ultrasound inhibits chondrocyte senescence by inhibiting PI3K/AKT/mTOR signaling.

Cellular senescence is an important cause of age-related degenerative diseases, including osteoarthritis (OA). Chondrocyte senescence is crucial in OA onset and progression. As a non-invasive, safe, and widely used physical rehabilitation factor, the effect and mechanism of low intensity pulsed ultrasound (LIPUS) on chondrocyte senescence remain unclear. This study evaluated the inhibitory effect of LIPUS on OA chondrocyte senescence in vitro and in vivo. The effect of LIPUS on chondrocyte senescence was examined by RT-qPCR, enzyme-linked immunosorbent assay (ELISA), and western blotting. Chan…

Suppression of early pro-inflammatory senescent signature post-radiotherapy mitigates chronic bone damage.

UNLABELLED: Cellular senescence has been implicated in the pathophysiology of radiotherapy-related bone loss. Based on our previous work, clearance of senescent cells using genetic and pharmacological tools alleviates the anomalies associated with radiation-associated bone deterioration. The pro-inflammatory senescence associated secretome referred to as senescence associated secretory phenotype (SASP), is a hallmark of cellular senescence. The modulation of SASP by senomorphic drugs, potentially can suppress the pro-inflammatory secretome of senescent cells, irrespective of the underlying sen…

Magnesium Attenuates Renal Senescence and Fibrosis With Reduced DNA Damage Response and H3K4me3 Enrichment at the p16INK4a Promoter.

Renal fibrosis is a final pathway leading to end-stage renal disease, with cellular senescence contributing to fibrosis and inflammation. Magnesium ions (Mg2+) are implicated in DNA stabilization and epigenetic regulation. In this study, we hypothesized that Mg2+ ameliorates renal fibrosis in association with reduced DNA damage responses and injury-induced cellular senescence, along with altered histone H3K4 trimethylation. To test this, we used murine models of radiation-induced organ injury and renal ischemia-reperfusion injury (IRI), along with primary cultured mouse renal proximal tubular …

STAT6 Targets the Autophagy Pathway to Regulate Microglial Senescence in Cognitive Impairment Caused by Cerebral Small-Vessel Disease.

Cerebral small-vessel disease (CSVD) represents a major etiology of vascular cognitive impairment (VCI), driven by pathological processes such as cellular senescence and neuroinflammation. Among these, microglia-the brain's specialized immune cells-play a key role in driving neuroinflammation through their senescence, thereby exacerbating cognitive dysfunction. Although signal transducer and activator of transcription 6 (STAT6) activation has been implicated in alleviating neuroinflammation and cognitive deficits in CSVD, the underlying mechanisms remain unclear. This study sought to elucidate…

TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.

BACKGROUND: Although recent studies provide mechanistic understanding to the pathogenesis of radiation induced lung injury (RILI), rare therapeutics show definitive promise for treating this disease. Type II alveolar epithelial cells (AECII) injury in various manner results in an inflammation response to initiate RILI. RESULTS: Here, we reported that radiation (IR) up-regulated the TNKS1BP1, causing progressive accumulation of the cellular senescence by up-regulating EEF2 in AECII and lung tissue of RILI mice. Senescent AECII induced Senescence-Associated Secretory Phenotype (SASP), consequen…

AS1041, a novel derivative of marine natural compound Aspergiolide A, induces senescence of leukemia cells via oxidative stress-induced DNA damage and BCR-ABL degradation.

Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of BCR-ABL tyrosine kinase. Imatinib was approved for CML therapy, however, BCR-ABL-dependent drug resistance, especially BCR-ABL-T315I mutation, restricts its clinical application. In this study, we reported anthraquinone lactone AS1041, a synthesized derivative of marine natural compound Aspergiolide A, showed anti-leukemia effect in vitro and in vivo by promoting cell senescence. Mechanistic study revealed the pro-senescence effect of AS1041 was dependent on oxidative stress-induced DNA damage, and the result

p38 (MAPK) stress signalling in replicative senescence in fibroblasts from progeroid and genomic instability syndromes.

Werner Syndrome (WS) is a human segmental progeria resulting from mutations in a DNA helicase. WS fibroblasts have a shortened replicative capacity, an aged appearance, and activated p38 MAPK, features that can be modulated by inhibition of the p38 pathway. Loss of the WRNp RecQ helicase has been shown to result in replicative stress, suggesting that a link between faulty DNA repair and stress-induced premature cellular senescence may lead to premature ageing in WS. Other progeroid syndromes that share overlapping pathophysiological features with WS also show defects in DNA processing, raising…

Нацеливание на прорастающую микроглию в прогрессивном множественном склерозе: подход, основанный на геронаучной информации.

Множественный склероз (MS) — нервно-воспалительное и нейродегенеративное расстройство центральной нервной системы (КНС). Возраст является самым сильным прогнозом фенотипа заболеваний, при этом большинство пожилых людей переходят к прогрессивной форме, характеризующейся необратимым неврологическим спадом. Эта клиническая прогрессия связана с охлаждением, отсеиванием CNS воспаления и нейродегенерацией, для которых в настоящее время не существует эффективных методов лечения, позволяющих регулировать заболевания. Клеточная сенесцензия, характеризующаяся секрецией посредников, выступающих за воспла

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disorder of the central nervous system (CNS). Age is the strongest pred … tion and neurodegeneration, for which there are currently no effective disease-modifying therapies. Cellular senescence, characterized by the secretion of pro-inflammatory mediators collectively known as the senescence-associated secretory phenotype (SASP), increases with age and contributes to tissue injury. In MS, neuroinflammation can further promote cellular sene …

Procyanidin B2 targeted CCR7 expression to inhibit the senescence-associated secretory phenotype through the NF-κB pathway to promote osteogenic differentiation of periodontal ligament stem cells in periodontitis.

Periodontitis is recognized as a chronic inflammatory disease, with aging emerging as a significant risk factor. Cellular senescence plays a crucial role in the biological process of aging. The senescence-associated secretory phenotype (SASP) is characterized by a series of pro-inflammatory factors, chemokines, and proteases, which are hallmark characteristics of senescent cells. These factors collectively alter the local environment, impacting the function of periodontal ligament stem cells (PDLSCs). Procyanidin B2 (PB2), the main dimer of oligomeric procyanidins, possesses antioxidant, anti-…

Context-dependent duality of senescent cells in liver fibrosis.

Liver fibrosis, marked by excessive deposition of extracellular matrix (ECM), is a critical precursor to cirrhosis, liver failure, and hepatocellular carcinoma. Accumulating evidence highlights that cellular senescence, characterized by stable cell-cycle arrest and senescence-associated secretory phenotypes (SASPs), is a key regulator of the fibrotic process. This review systematically dissects the context-dependent roles of senescent cells in liver fibrosis, with a focus on hepatocytes, hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells, and natural kille…

Targeting anti-apoptotic pathways eliminates senescent melanocytes and leads to nevi regression.

Human melanocytic nevi (moles) result from a brief period of clonal expansion of melanocytes. As a cellular defensive mechanism against oncogene-induced hyperplasia, nevus-resident melanocytes enter a senescent state of stable cell cycle arrest. Senescent melanocytes can persist for months in mice and years in humans with a risk to escape the senescent state and progress to melanoma. The mechanisms providing prolonged survival of senescent melanocytes remain poorly understood. Here, we show that senescent melanocytes in culture and in nevi express high level of the anti-apoptotic BCL-2 family

Prognostic significance of therapy-induced senescence and SASP dynamics in acute myeloid leukemia: a retrospective cohort study.

BACKGROUND: Chemotherapy constitutes the backbone of Acute Myeloid Leukemia (AML) treatment but often induces cellular senescence. While senescence initially halts tumor proliferation, the accumulation of senescent cells and the Senescence-Associated Secretory Phenotype (SASP) may promote leukemic survival and relapse. The clinical correlation between post-treatment senescence burden and AML prognosis remains poorly characterized. METHODS: We conducted a single-center retrospective study analyzing 128 newly diagnosed AML patients treated with standard induction chemotherapy between January 20…

Senescence and SASP Are Potential Therapeutic Targets for Ischemic Stroke.

Aging is a known co-morbidity of ischemic stroke with its risk and severity increasing every year past 55+. While many of the current stroke therapies have shown success in reducing mortality, post-stroke morbidity has not seen the same substantial reduction. Recently, the involvement of cellular senescence and SASP in brain injury and neurological degeneration has been recognized. Ischemic injury causes oxidative stress and mitochondrial damage that induces senescence through the activation of p21 and p16 pathways, ultimately leading to synthesis and release of senescence-associated secretory…

The SIRT5-SUCLG2 desuccinylation axis delays ovarian aging via a mitochondrial-epigenetic regulatory mechanism.

Mitochondrial dysfunction and epigenetic alterations play critical roles in aging-related diseases, yet the molecular mechanisms linking mit … and K101 enhanced its protein stability and activity, thereby improving mitochondrial function upon cellular senescence. However, SUCLG2 hypersuccinylation specifically increased H4K8ac through acetyl-CoA accumulation in nucleus, leading to the overexpression of metabolism-related genes to compensate for the energy demand deficiency caused by decreased mitochondrial …

A continuous DNA repairing system for alleviating intervertebral disc degeneration.

DNA damage triggering senescence-associated secretory phenotype (SASP) is a key pathway of Intervertebral Disc Degeneration (IVDD). Current … arkedly alleviated IVDD. This study presents a promising approach to reverse the DNA damage-induced cellular senescence and IVDD, providing a repair strategy for addressing diseases associated with DNA damage and cellular senescence.