Результаты поиска

A senescence-responsive nanodrug amplifies radiotherapy efficacy.

Radiotherapy (RT) is a mainstay of cancer treatment but is limited by tumor resistance and off-target tissue damage, often mediated by therapy-induced cellular senescence. Here, we developed a "one-two punch" nanodrug, Lipo@ABT263@Au, that integrated a senolytic agent (ABT-263) with a gold-shelled liposome for radiosensitization and sustained drug release. High-throughput screening and transcriptomic analysis identified senescence as a key RT-induced vulnerability. In vitro, Lipo@ABT263@Au eliminated senescent tumor cells, enhanced RT-induced apoptosis, and suppressed the pro-tumorigenic effec…

Микроглиатоподобные чувствительности ограничивают ремиилизацию через сенсацию, связанную с фенотипом фенория.

Способность регенерировать миелин в центральной нервной системе снижается с возрастом. Это сокращение особенно заметно в случае множественного склероза (MS), хронического заболевания демиелином. Независимо от того, способствует ли клеточная сенсация, являющаяся отличительной чертой старения, нарушению воспоминаний, до сих пор неизвестно. Здесь мы показываем, что яркие клетки накапливаются в демиелинированных повреждениях после травмы, а лечение сенолитами усиливает ремиэлизацию у молодых и средних мышей, но не пожилых мышей. В юных мышах мы наблюдаем за тем, как корректируются стенограммы, свя

Совпадение в аннотации оригинала
The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident in multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesi…

Royal jelly suppresses senescence-associated secretory phenotype in senescent human epidermal keratinocytes.

BACKGROUND: Royal Jelly (RJ) is widely used in cosmetics for its beneficial skin effects, but its impact on cellular senescence remains unclear. Senomorphic agents that suppress the senescence-associated secretory phenotype (SASP) offer safe therapeutic strategies for skin aging. This study investigates the senomorphic effects of RJ on epidermal senescence. METHODS AND RESULTS: We utilized an in vitro replicative senescence model of normal human epidermal keratinocytes, validating our findings with cells from chronologically aged adult donors, including a 75-year-old. Results demonstrated tha…

Theophylline alleviates cyclophosphamide-induced T cell senescence by downregulating acetylation of p53 at lysine 373.

Cyclophosphamide is a widely used immunosuppressive and chemotherapeutic agent in clinics. Previous studies have indicated that cyclophosphamide treatment induces cellular senescence in patients, although the underlying mechanisms remain elusive. Here, we reported that cyclophosphamide induced T cell senescence in the spleen of mice. Meanwhile, phosphoramide mustard cyclohexanamine (PM), an active metabolite of cyclophosphamide, triggered human T cell senescence. RNA sequencing analysis revealed that PM promoted senescence of primary human T cells through the activation of the p53 signaling pa…

5-aza-2'-deoxycytidine-mediated c-myc Down-regulation triggers telomere-dependent senescence by regulating human telomerase reverse transcriptase in chronic myeloid leukemia.

Increased proliferation rates as well as resistance to apoptosis are considered major obstacles for the treatment of patients with chronic myelogenous leukemia (CML), thus highlighting the need for novel therapeutic approaches. Since senescence has been recognized as a physiological barrier against tumorigenesis, senescence-based therapy could represent a new strategy against CML. DNA demethylating agent 5-aza-2'-deoxycytidine (DAC) was reported to induce cellular senescence but underlying mechanisms remain to be elucidated. Here, we report that exposure to DAC triggers senescence in chronic l…

The Aging Microenvironment Shapes Angiogenic Remodeling in IBD-Associated Colorectal Carcinogenesis.

Chronic intestinal inflammation establishes a pro-senescent microenvironment that fuels the stepwise evolution from inflammatory bowel disease (IBD) to colorectal cancer. Although cellular senescence initially functions as a tumor-suppressive barrier, the persistent accumulation of senescent cells can promote disease progression through the senescence-associated secretory phenotype (SASP). Key SASP mediators, including VEGF, IL-8/CXCL8, and matrix metalloproteinases (MMPs), reprogram endothelial and stromal compartments, driving aberrant neovascularization, vascular leakiness, extracellular-ma…

Cdkn1a silencing restores myoblast differentiation by inducing selective apoptosis in senescent cells.

BACKGROUND: Sarcopenia, characterized by a progressive loss of skeletal muscle mass and function, is associated with the accumulation of senescent muscle stem cells, which impair muscle regeneration and contributes to the decline in muscle health. Cdkn1a, which encodes p21, is a well-known marker of cellular senescence. However, it remains unclear whether p21 inhibition eliminates senescent myoblasts and restores the differentiation capacity. METHODS: We performed transcriptomic analysis to identify genes related to aging-induced sarcopenia using 21 month-old Sprague-Dawley rats. To investiga…

Lysosomal Dysfunction Is Associated With Intervertebral Disc Degeneration: Multiomics and Machine Learning Identify Molecular Subtypes and Hub Genes.

Intervertebral disc degeneration (IVDD) is closely associated with cellular senescence and defective autophagic degradation, but the molecular heterogeneity and functional significance of lysosome-related alterations remain incompletely understood. We integrated bulk transcriptomic datasets (GSE56081 and GSE70362) and single-cell RNA-sequencing data (GSE153066) using consensus clustering, weighted gene coexpression network analysis, machine-learning algorithms, immune-signature analysis, and covariate-adjusted correlation testing. Candidate genes were evaluated in human and rat disc tissues, a…

Modeling and Characterization of Intestinal Senescence Using Human Organoids: Insights Into the Epithelial to Mesenchymal Transition.

Intestinal senescence is an important factor in systemic aging and age-related diseases; however, detailed studies have been limited due to the lack of robust experimental models. In this study, we established cellular senescence models of human small intestinal organoids using two senescence-inducing agents: butyrate (an endogenous microbial metabolite) and cisplatin (an exogenous chemotherapeutic agent). Both molecules induced senescence-associated features, including increased p16INK4a, CDKN1A, IL8, and TNF expression, as well as SA-β-Gal activity. RNA-sequencing revealed that cisplatin, bu…

Blue Light Exposure Induces Changes Associated With Senescence and Skin Aging in Human Dermal Fibroblasts.

Blue light is becoming increasingly prevalent in our daily lives. However, the possible deleterious effects of blue light exposure on the skin have been largely overlooked. We have previously shown that blue light has the ability to induce mitochondrial DNA (mtDNA) damage and dysfunction in human dermal fibroblasts (HDFn). However, whether blue light is able to induce senescence in skin has yet to be investigated. Cellular senescence is a key part of the aging process and is heavily associated with an aging phenotype. Our study involved exposing HDFn to varying doses of blue light before asses…

The right time, the right cell: the potential for precision senotherapy in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy driven by proinflammatory signaling that leads to pulmonary vascular remodeling and ultimately, right ventricular failure. Existing therapies fail to eliminate dysfunctional cells or reverse pathologic remodeling. Cellular senescence, a state of persistent cell-cycle arrest coupled with proinflammatory signaling, has emerged as a compelling, yet complex, contributor to PAH pathophysiology. Human data indicate that senescent cells accumulate within remodeled pulmonary vascular lesions and may promote proliferation and apoptosis resis…

Thiourea-Based H2S-Releasing Pramipexole Hybrids as Neuroprotective Agents.

Multitarget hybrid molecules are a promising strategy for treating complex neurodegenerative disorders such as Parkinson's disease (PD), where dopaminergic dysfunction, oxidative stress, neuroinflammation, and cellular senescence coexist and drive disease progression. Here, we developed pramipexole-derived hydrogen sulfide (H2S)-releasing hybrids using, for the first time, a thiourea moiety as an H2S-donating linker to extend the therapeutic profile of pramipexole beyond dopamine receptor agonism. The hybrids were synthesized and characterized, and their H2S-releasing properties were assessed …

The endoplasmic reticulum protein HSPA5/BiP is essential for decidual transformation of human endometrial stromal cells.

Decidualization denotes the process of inflammatory reprogramming of endometrial stromal cells (EnSC) into specialized decidual cells (DC). During this process, EnSC are subjected to endoplasmic reticulum (ER) stress as well as acute cellular senescence. Both processes contribute to the proinflammatory mid-luteal implantation window and their dysregulation has been implicated in reproductive failure. Here, we evaluated the link between ER stress, decidual differentiation and senescence. In-silico analysis identified HSPA5 gene, codifying the ER chaperone BiP, as a potentially critical regulato…

The Secretome Derived From Human Umbilical Cord Mesenchymal Stem Cells Improves Skin Photoaging by Enhancing Mitophagy to Inhibit the cGAS-STING Pathway.

Ultraviolet (UV)-induced skin photoaging is driven by cellular senescence and chronic inflammation. Although the secretome (SCT) derived from human umbilical cord mesenchymal stem cells (hUC-MSC SCT) exhibits regenerative potential, its role in combating photoaging remains to be elucidated. In this study, we show that SCT markedly ameliorates photoaging in UV-exposed mice, restoring epidermal barrier function, dermal collagen integrity, senescence-associated markers, and systemic inflammatory profiles. In UVB-irradiated human immortalized keratinocytes (HaCaT), SCT enhanced cellular viability,…

Benzo(a)pyrene induces cardiac hypertrophy via the aryl hydrocarbon receptor-mediated DNA damage.

Benzo(a)pyrene (BaP), one of the most extensively studied polycyclic aromatic hydrocarbons, is prevalent in the environment. BaP exposure has been linked to cardiovascular diseases, but the underlying mechanisms remain elusive. In this study, we observed that BaP exposure induces cardiac hypertrophic effects (enlarged cell surface area and increased expression of Nppa, Nppb, and Myh7) in rat H9c2 cardiomyoblasts. Notably, these effects are dependent on the aromatic hydrocarbon receptor (AHR)-Cyp1a1/Cyp1b1 axis. AHR-Cyp1a1/Cyp1b1 signaling also mediates BaP-induced cellular senescence, evidence…

Acceleration of melanocyte senescence by the proinflammatory cytokines IFNγ and TNFα impairs the repigmentation response of vitiligo patients to narrowband ultraviolet B (NBUVB) phototherapy.

Vitiligo is a chronic autoimmune disease characterized by the T helper 1 (Th1) cytokine-driven immune destruction of melanocytes (MCs). Although narrowband ultraviolet B (NBUVB) phototherapy has been proven to be an effective therapeutic option, the repigmentation response to that phototherapy varies greatly in different vitiligo patients. Here, we demonstrate that there is an increase of NBUVB-induced cellular senescence in vitiligo MCs exposed to Th1 cytokine interferon γ (IFNγ) and/or tumor necrosis factor α (TNFα) in lesional vitiligo skin from poor responders who had undergone NBUVB photo…

The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment.

The gut microbiota is suspected to promote colorectal cancer (CRC). Escherichia coli are more frequently found in CCR biopsies than in healthy mucosa; furthermore, the majority of mucosa-associated E. coli isolated from CCR harbors the pks genomic island (pks+ E. coli) that is responsible for the synthesis of colibactin, a genotoxic compound. We have recently reported that transient contact of a few malignant cells with colibactin-producing E. coli increases tumor growth in a xenograft mouse model. Growth is sustained by cellular senescence that is accompanied by the production of growth facto…

Mesenchymal stem cells derived from the fibrotic tissue of atrophic nonunion or the bone marrow of iliac crest: A donor-matched comparison.

PURPOSE: Atrophic nonunion is one of the most difficult complications of fracture. The cellular factors that contribute to atrophic nonunion … bent assay (ELISA) assessment was applied to evaluate the paracrine function of AN-MSCs or IC-MSCs. Cellular senescence of AN-MSCs or IC-MSCs was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. RESULTS: AN-MSCs or IC-MSCs from the four donors showed morphologic and immunophenotypic characteristics of MSCs, with the expression of MSCs marke …

A multi-scale framework to advance experimental models of skin aging.

Skin aging is a multifactorial, multiscale process driven by the interplay between intrinsic cellular decline and extrinsic environmental exposures. Increasing evidence positions the skin as a dynamic interface and sensitive "window" reflecting systemic aging. However, research remains fragmented across scales, and existing models fail to capture the full complexity of systemic regulation. In this review, we introduce a hierarchical four-dimension framework of skin aging to systematically benchmark experimental models against core aging hallmarks. This framework integrates: (i) molecular and c

ETS2 targets ZMYND11 to inhibit thyroid cancer progression via the mTOR signaling pathway.

BACKGROUND: Despite advancements in thyroid cancer (THCA) treatment, the prognosis for advanced cases remains poor. Cellular senescence is crucial in tumor progression, with ETS2 emerging as a key regulator. However, the role of ETS2 and its interaction with ZMYND11 in THCA is unclear. METHODS: Differentially expressed genes (DEGs) connected with cellular senescence were determined from The Cancer Genome Atlas (TCGA)-THCA dataset. Functional analysis, prognostic risk model, and nomogram were then performed to identify ETS2 as a hub gene. The roles of ETS2 and ZMYND11 were explored using Weste…