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Single-cell transcriptomic analysis of the senescent microenvironment in bone metastasis.

Bone metastasis (BM) is a mortality-related event of late-stage cancer, with non-small cell lung cancer (NSCLC) being a common origin for BM … properties. The endothelial-mesenchymal transition involved with SOX18 activation is related to the cellular senescence of vascular endothelial cells from BM. CD4Tstr cells, with pronounced stress and senescence states, are preferentially infiltrated in BM, indicating stress-related dysfunction contributing to the immunocompromised environment during tumour metastasi …

Blocking PD-L2 prevents senescent cell accumulation and age-related dysfunction.

Senescent cells, which are normally cleared by the immune system but accumulate with age, contribute to multiple disorders including metabolic dysfunction and impaired fitness. While immune checkpoint inhibitors have been well studied in cancer, the role of programmed cell death ligand 2 (PD-L2) in non-cancerous, age-associated cellular senescence remains unclear. We found that PD-L2 is upregulated in isolated senescent human cells and during aging, and senolytics can remove age-associated, highly PD-L2-expressing senescent cells. Old PD-L2 knockout mice accumulate fewer senescent cells than o…

Placental Senescence and the Two-Stage Model of Preeclampsia.

In this review, we summarize how an increasingly stressed and aging placenta contributes to the maternal clinical signs of preeclampsia, a potentially lethal pregnancy complication. The pathophysiology of preeclampsia has been conceptualized in the two-stage model. Originally, highlighting the importance of poor placentation for early-onset preeclampsia, the revised two-stage model explains late-onset preeclampsia as well, which is often preceded by normal placentation. We discuss how cellular senescence in the placenta may fit with the framework of the revised two-stage model of preeclampsia …

DNA damage response in vascular endothelial senescence: Implication for radiation-induced cardiovascular diseases.

A post-exposure cohort study in Hiroshima and Nagasaki reported that low-dose exposure to radiation heightened the risk of cardiovascular diseases (CVD), such as stroke and myocardial infarction, by 14-18% per Gy. Moreover, the risk of atherosclerosis in the coronary arteries reportedly increases with radiation therapy of the chest, including breast and lung cancer treatment. Cellular senescence of vascular endothelial cells (ECs) is believed to play an important role in radiation-induced CVDs. The molecular mechanism of age-related cellular senescence is believed to involve genomic instabilit…

Integrin β3 Promotes Retinal Neovascularization via Endoplasmic Reticulum Stress-Mediated Endothelial Cell Senescence.

PURPOSE: Integrin β3 (ITGB3/Itgb3), a transmembrane receptor implicated in cell adhesion and signaling, may regulate cellular senescence. We hypothesized that ITGB3 drives retinal neovascularization (RNV) through endoplasmic reticulum stress (ERS)-mediated endothelial cell (EC) senescence and aimed to delineate the underlying molecular mechanisms. METHODS: Retinal vascular EC subpopulations were profiled by single-cell RNA sequencing (scRNA-seq) in an oxygen-induced retinopathy (OIR) model. Immunofluorescence staining further confirmed P21 and Integrin β3 expression. Human retinal microvascul…

A Review of Ionizing Radiation-Induced Senescence of Bone Marrow Mesenchymal Stem/Stromal Cells: Mechanisms and Therapeutic Strategies.

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are important components of bone marrow, possessing multipotent differentiation potenti … of IR on BM-MSCs, this review systematically summarizes the general mechanisms of radiation-induced cellular senescence, examines the effects of different radiation types (e.g., gamma rays, X-rays, and heavy-ion radiation) and doses on BM-MSCs senescence, and outlines senotherapeutic strategies targeting BM-MSCs senescence. The analysis indicates that the senescence …

[Cellular ageing, ageing and cancer].

Cellular division is essential for the survival of the multicellular organisms which contain renewable tissues. However, cellular division also puts the organisms in danger to develop any types of cancers. Cellular senescence has emerged in part as a tumor suppressor mechanism. Here we discuss the function and regulation of the tumor suppressor proteins INK4a/ARF in connection with replicative senescence, cancer and aging. double dagger.

Tryptanthrin targets GSTP1 to induce senescence and increases the susceptibility to apoptosis by senolytics in liver cancer cells.

Targeting senescence has emerged as a promising strategy for liver cancer treatment. However, the lack of a safe agent capable of inducing complete senescence and being combined with senolytics poses a limitation. Here, we screened a natural product library and identified tryptanthrin (TRYP) as a potent inducer of cellular senescence in liver cancer cells both in vitro and in vivo. Mechanistically, Glutathione S-transferase P1 (GSTP1), a key regulator for redox homeostasis, was identified as a target protein for TRYP-induced senescence. TRYP directly bound to GSTP1 and inhibited its enzymatic …

Sub-lethal doses of chemotherapeutic agents induce senescence in T cells and upregulation of PD-1 expression.

Cellular senescence is a stable cell cycle arrest, usually in response to internal and/or external stress, including telomere dysfunction, abnormal cellular growth, and DNA damage. Several chemotherapeutic drugs, such as melphalan (MEL) and doxorubicin (DXR), induce cellular senescence in cancer cells. However, it is not clear whether these drugs induce senescence in immune cells. We evaluated the induction of cellular senescence in T cells were derived from human peripheral blood mononuclear cells (PBMNCs) in healthy donors using sub-lethal doses of chemotherapeutic agents. The PBMNCs were ke…

Synergistic roles of CBX4 chromo and SIM domains in regulating senescence of primary human osteoarthritic chondrocytes.

BACKGROUND: Cellular senescence is a critical factor contributing to osteoarthritis (OA). Overexpression of chromobox homolog 4 (CBX4) in a mouse system was demonstrated to alleviate post-traumatic osteoarthritis (PTOA) by reducing cellular senescence. Additionally, replicative cellular senescence of WI-38 fibroblasts can be attenuated by CBX4. However, the mechanisms underlying this senomorphic function of CBX4 are not fully understood. In this study, we aimed to investigate the role of CBX4 in cellular senescence in human primary osteoarthritic chondrocytes and to identify the functional dom…

LCN2 promotes HEI-OC1 cells senescence via activating NF-κB signal pathway in presbycusis.

Presbycusis, or age-related hearing loss (ARHL), is a prevalent sensory disorder in the elderly, driven by genetic factors, oxidative stress, inflammation responses, and cellular senescence. Despite its significance, the molecular mechanisms underlying ARHL remain poorly defined. In this study, we employed bioinformatic analysis of public gene expression datasets to identify differentially expressed genes in ARHL. Protein-protein interaction network analysis further nominated LCN2 as a hub gene. Experimental validation in aging C57BL/6J mice and HEI-OC1 auditory cells revealed that elevated LC…

Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways.

OBJECTIVES: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients. METHODS: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed. Synovial tissue specimens from patients with inflammatory arthritis and aorta tissue were used as disease control samples. Senescent…

Robust immune cell infiltration and macrophage senescence occur within a week of recovery after limb immobilization in older adult skeletal muscle.

Immune cells are critical for modulating inflammation and extracellular matrix remodelling for effective muscle regrowth following disuse atrophy. However, disrupted macrophage function and accumulation of cellular senescence may limit muscle recovery in ageing. The present study aimed to compare changes in the cellular dynamics of muscle macrophages, cellular senescence and collagen content during early recovery following 14 days of unilateral limb immobilization in young (n = 18; ∼24 years) and older male and female adults (n = 18; ∼69 years). Participants underwent 14 days of immobilization…

Aging as the degradation of conjunctive coupling: A triadic framework S = F × E × N for biological senescence.

Despite the landmark identification of twelve hallmarks of aging (López-Otín et al., 2023), geroscience lacks a formal account of why these hallmarks interact and amplify each other, why mono-target interventions show systematically limited efficacy, and what determines the threshold at which compensatory mechanisms fail. A recent extension of the hallmarks framework has further integrated psychosocial and social determinants of aging (López-Otín & Kroemer, 2025; Kroemer et al., 2025), reinforcing the need for an architectural account that can accommodate both molecular and environmental modul

Nanoparticle-Based Tools to Study Hallmarks of Aging at the Molecular Level.

Aging is characterized by the cumulative damage to the genome, proteome, epigenome, and organelles, which ultimately leads to telomere attrition, loss of proteostasis, genomic instability, mitochondrial dysfunction, cellular senescence, altered intracellular communication, chronic inflammation, and dysregulated nutrient sensing. Nanoparticle-based technologies are revolutionizing the ability to study the hallmark of aging at the molecular level. Due to the key limitation of conventional genomic, epigenomic, transcriptomic, proteomic, and metabolomic tools, nanoparticles play a vital role in th…

Adrenal cortex senescence: an ageing-related pathology?

The adrenal glands are a pair of endocrine organs that produce and secrete mineralocorticoids, glucocorticoids, sex hormones, adrenaline, and noradrenaline. They have a vital role in a range of physiological processes including regulating electrolyte balance, blood pressure and metabolism, immunomodulation, sexual development and the stress response. Adrenal cortex senescence describes the ageing-related decline in the normal functioning of the adrenal cortex, characterised by an alteration in the output of adrenal cortical hormones, in particular reduced secretion of dehydroepiandrosterone (D

Pathological aging is alleviated by neutralization of the autophagy-repressive tissue hormone DBI/ACBP.

DBI/ACBP (diazepam binding inhibitor, acyl CoA-binding protein) is a macroautophagy/autophagy-inhibitory tissue hormone produced by multiple … al aging induced by cisplatin or doxorubicin, DBI/ACBP neutralization suppresses renal fibrosis and cellular senescence. Similarly, in cardiac and hepatic aging models, anti-DBI/ACBP reduces expression of the senescence marker CDKN1A/p21 (cyclin dependent kinase inhibitor 1A) in cardiomyocytes and hepatocytes. Single-nucleus RNA sequencing of heart tissue revealed th …

Иммунонесцензия в множестве склерозов: новые идеи и клинические последствия.

Старение ассоциируется с глубокими изменениями в клеточной функции (созревание) и влияет на различные ткани и системы, включая иммунную систему (иммунонесценность). Несмотря на рост среднего возраста лиц с множественным склерозом (MS), мало что известно о том, что происходит с иммунной системой пожилых людей с MS или о воздействии иммуномумудуляторного и иммуновосприимчивого лечения MS на стареющую иммунную систему. В этом тематическом обзоре мы обсуждаем концепции физиологической клеточной сенсации и иммуносенсии, а также анализируем последние имеющиеся данные об иммунной сенсеменности в MS.

Совпадение в аннотации оригинала
Aging is associated with profound changes in cellular function (senescence) and affects various tissues and systems, including the immune sy … for MS on the aging immune system. In this topical review, we discuss the concepts of physiological cellular senescence and immunosenescence, and we review the latest available data on immunosenescence in MS. We examine evidence suggesting premature aging of the immune system in MS, including premature aging of T cells, reduced numbers of naïve lymphocytes, expansion …

The impact of ageing mechanisms on musculoskeletal system diseases in the elderly.

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevale…

Senescence and extracellular vesicles: novel partners in vascular amyloidosis.

OBJECTIVES: School disengagement (SD) is associated with mental health, educational, and behavioral challenges. This study explored temporal changes in SD and SD rates among children with mental health conditions (MHCs) in a representative sample of US children aged 6 to 17 years from 2018 to 2022 and identified SD correlates. METHODS: We analyzed cross-sectional National Survey of Children's Health (NSCH) data from 2018 and 2019 (pre-pandemic), 2020 (lockdown), and 2021 and 2022 (intra-pandemic) (N = 136 576). We defined SD using an NSCH-developed measure based on parent responses regarding