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Oxidative stress, cardiomyocytes premature senescence and contractile dysfunction in in vitro and in vivo experimental models of Chagas disease.

AIMS: The relationship between redox imbalance and cardiovascular senescence in infectious myocarditis is unknown. Thus, the aim of this study was to investigate whether cardiomyocytes parasitism, oxidative stress and contractile dysfunction can be correlated to senescence-associated β-galactosidase (SA-β-Gal) activity in Trypanosoma cruzi-infection in vitro and in vivo. METHODS: Uninfected, T. cruzi-infected untreated and benznidazole (BZN)-treated H9c2 cardiomyocytes and rats were investigated. Parasitological, prooxidant, antioxidant, microstructural, and senescence-associated markers were

Association between endometrial senescent cells and immune cells in women with repeated implantation failure.

PURPOSE: The aim of this study was to compare women with recurrent implantation failure (RIF) and control group in terms of the associations between p16-positive senescent cells and certain types of immune cells in human endometrium during the mid-luteal phase METHODS: Immunohistochemical staining was performed in 116 endometrial biopsies taken from 57 women presenting RIF, and control group of 59 women who became pregnant after the first intracytoplasmic sperm injection. Endometrial tissue sections were stained immunohistochemically for p16 (Senescent cells), CD4 (T-helpers), CD8 (T-killers),

The Immunogenicity of Human Senescent Cells Is Dependent on the Senescence Inducer and Cell Type.

Senescent cells accumulate with age and after exposure to various stresses, contributing to chronic diseases and cancer, effects largely driven by the senescence-associated secretory phenotype (SASP). Recent evidence indicates that a subset of senescent cells exhibits immunogenic properties. However, the extent to which immunogenicity depends on the cell type and the senescence inducer remains unclear. In this study, we evaluated the immunogenic properties of various human cell types induced to senesce following exposure to ionizing radiation (IR) or oncogenic RAS. Specifically, we used human

IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis.

Senescent cells (SnCs) are implicated in the pathogenesis of age-related diseases including osteoarthritis (OA), in part via expression of a senescence-associated secretory phenotype (SASP) that includes immunologically relevant factors and cytokines. In a model of posttraumatic OA (PTOA), anterior cruciate ligament transection (ACLT) induced a type 17 immune response in the articular compartment and draining inguinal lymph nodes (LNs) that paralleled expression of the senescence marker p16INK4a (Cdkn2a) and p21 (Cdkn1a). Innate lymphoid cells, γδ+ T cells, and CD4+ T cells contributed to IL-1

Accelerated replicative senescence of ataxia-telangiectasia skin fibroblasts is retained at physiologic oxygen levels, with unique and common transcriptional patterns.

The genetic disorder, ataxia-telangiectasia (A-T), is caused by loss of the homeostatic protein kinase, ATM, and combines genome instability, tissue degeneration, cancer predisposition, and premature aging. Primary fibroblasts from A-T patients exhibit premature senescence when grown at ambient oxygen concentration (21%). Here, we show that reducing oxygen concentration to a physiological level range (3%) dramatically extends the proliferative lifespan of human A-T skin fibroblasts. However, they still undergo senescence earlier than control cells grown under the same conditions and exhibit hi

Targeted clearance of senescent cells alleviates alcohol-associated liver disease by restoring cellular function and immune balance.

The liver is one of the organs most affected by alcohol consumption, and its interaction with aging is particularly significant. Chronic alcohol consumption accelerates liver aging through mechanisms such as oxidative stress, inflammation, fibrosis, and impaired regeneration. It is still unknown whether senescent cell clearance orchestrates innate and adaptive immune responses during the alcohol-induced old liver damage process. To investigate this, we used INK-ATTAC transgenic mice treat with AP20187 (AP) to eliminate p16Ink4a-positive senescent cells in chronic-plus-binge ethanol feeding mod

Kaempferol alleviates T-cell immunosenescence and inflammaging in aged mice via the SIRT3-LKB1-AMPK-mitophagy pathway.

BACKGROUND: Immunosenescence, characterized by progressive immune dysfunction accompanied by chronic low-grade inflammation (inflammaging), is a key driver of systemic ageing. Senescent T cells are central to this process, yet effective interventions remain limited. Kaempferol is a natural flavonoid with diverse bioactivities, but its potential to counteract T-cell immunosenescence is largely unexplored. Here, we investigated whether kaempferol alleviates T-cell immunosenescence and inflammaging in aged mice and delineated the underlying mechanism. METHODS: Nineteen-month-old C57BL/6 J mice we

Теломер Динамикс в иммунном сознании и истощении, вызванном хроническим вирусным заражением.

Прогрессивная утрата иммунологической памяти во время старения коррелирует с снижением производительности и сокращением теломеров Т клеток. Растущие данные свидетельствуют о том, что этот фенотип повторяется во время хронической вирусной инфекции. Антигенный объем, навязанный стойкими и скрытыми вирусами, ставит иммунную систему в уникальное положение, которое приводит к истощению Т-клеток, характеризующееся нарушениями функций Т-клеток. У этих дисфункциональной памяти T клеток нет теломеразы, белка, способного расширять и стабилизировать хромосомные концы, что ограничивает динамику теломера.

Совпадение в аннотации оригинала
The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cell … lation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

Disrupted immune senescence in early pregnancy is associated with recurrent pregnancy loss.

BACKGROUND: Immune system adaptation plays a crucial role in pregnancy success. Cellular senescence, linked to immune dysfunction and chronic inflammation, may contribute to adverse pregnancy outcomes but remains poorly characterized during early gestation, at the systemic level. OBJECTIVE: To characterize senescence marker expression in peripheral leukocyte subsets in early pregnancy and to examine its association with miscarriage history and functionally distinct T helper cell populations. METHODS: This cross-sectional study included 52 pregnant women: 18 with recurrent pregnancy loss (≥2

Immune senescence: relative contributions of age and cytomegalovirus infection.

Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV) infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV) infection with or without t

ATM-deficient neural precursors develop senescence phenotype with disturbances in autophagy.

ATM is a kinase involved in DNA damage response (DDR), regulation of response to oxidative stress, autophagy and mitophagy. Mutations in the ATM gene in humans result in ataxi A-Telangiectasia disease (A-T) characterized by a variety of symptoms with neurodegeneration and premature ageing among them. Since brain is one of the most affected organs in A-T, we have focused on senescence of neural progenitor cells (NPCs) derived from A-T reprogrammed fibroblasts. Accordingly, A-T NPCs obtained through neural differentiation of iPSCs in 5% oxygen possessed some features of senescence including incr

Premature immunosenescence in HIV-infected patients on highly active antiretroviral therapy with low-level CD4 T cell repopulation.

OBJECTIVES: To analyse the role of thymic function and its association with cellular immunosenescence markers in patients with low-level CD4 T cell repopulation, despite complete HIV RNA replication control on highly active antiretroviral therapy (HAART). METHODS: Cellular immunosenescence markers comparing patients with CD4 T cell counts <or=250 cells/mm(3) for >or=48 weeks (n = 11) and patients with a CD4 T cell count >or=500 cells/mm(3) (n = 11) were investigated. Both groups were also compared with 11 healthy volunteers of similar age. Naive CD4 T cell counts, beta- and delta-T cell rearr

NF-κB-induced R-loop accumulation and DNA damage select for nucleotide excision repair deficiencies in adult T cell leukemia.

Constitutive NF-κB activation (NF-κBCA) confers survival and proliferation advantages to cancer cells and frequently occurs in T/B cell malignancies including adult T cell leukemia (ATL) caused by human T-cell leukemia virus type 1 (HTLV-1). Counterintuitively, NF-κBCA by the HTLV-1 transactivator/oncoprotein Tax induces a senescence response, and HTLV-1 infections in culture mostly result in senescence or cell-cycle arrest due to NF-κBCA How NF-κBCA induces senescence, and how ATL cells maintain NF-κBCA and avert senescence, remain unclear. Here we report that NF-κBCA by Tax increases R-loop

Non-small cell lung cancer is susceptible to induction of DNA damage responses and inhibition of angiogenesis by telomere overhang oligonucleotides.

Exposure of the telomere overhang acts as a DNA damage signal, and exogenous administration of an 11-base oligonucleotide homologous to the 3'-telomere overhang sequence (T-oligo) mimics the effects of overhang exposure by inducing senescence and cell death in non-small cell lung cancer (NSCLC) cells, but not in normal bronchial epithelial cells. T-oligo-induced decrease in cellular proliferation in NSCLC is likely directed through both p53 and its homolog, p73, with subsequent induction of senescence and expression of senescence-associated proteins, p21, p33(ING), and p27(Kip1) both in vivo a

Immunosenescence: a key player in cancer development.

Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. T cell-output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-li

Adenosine deaminase modulation of telomerase activity and replicative senescence in human CD8 T lymphocytes.

Increased proportions of CD8 T lymphocytes lacking expression of the CD28 costimulatory receptor have been documented during both aging and chronic infection with HIV-1, and their abundance correlates with numerous deleterious clinical outcomes. CD28-negative cells also arise in cell cultures of CD8(+)CD28(+) following multiple rounds of Ag-driven proliferation, reaching the end stage of replicative senescence. The present study investigates the role of a second T cell costimulatory receptor component, adenosine deaminase (ADA), on the process of replicative senescence. We had previously repor

T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.

T cell immunosenescence refers to the progressive functional decline of T lymphocytes with aging, characterized by the phenotypic markers, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP), representing a pivotal aspect of overall immune aging. This review systematically elucidates the critical role of T cell immunosenescence in the pathogenesis of common inflammatory skin diseases, including psoriasis, atopic dermatitis, rosacea, and seborrheic dermatitis. Senescent T cells drive the production of a disease-specific SASP via internally dysregulated signaling

Immunocyte senescence: A new perspective on the remodeling of the ovarian cancer microenvironment and therapeutic intervention.

Immune cell senescence in ovarian cancer manifests as distinct phenotypic alterations in T cells, natural killer (NK) cells, macrophages, and dendritic cells (DCs), alongside dynamic crosstalk with the tumor microenvironment (TME). This senescence contributes substantially to the high mortality and therapeutic resistance characteristic of ovarian carcinoma. Senescent immune cells develop a senescence-associated secretory phenotype (SASP), secreting pro-tumorigenic cytokines and chemokines that drive regulatory T cell (Treg) expansion, extracellular matrix (ECM) remodeling, and the establishmen

Age-associated Autoimmunity Driven by T cell Immunosenescence.

While certain autoimmune conditions are more common in the young (e.g. Type 1 Diabetes), others are more frequent in the aged. A striking example is chronic inflammatory demyelinating polyneuropathy (CIDP), a CD4+ T cell-mediated autoimmune disease of the peripheral nervous system, which has a peak decade of onset of 70-79 years. How aging predisposes to autoimmunity, however, remains unclear. CD4+ T cells are highly susceptible to age-associated changes, including acquisition of immunosenescent features such as enhanced SA-β-gal activity, increased Cdkn1a (p21) expression, and upregulation of

Immune resilience in HIV-infected individuals seronegative for cytomegalovirus.

OBJECTIVE: Low CD4/CD8 T-cell ratios occur in conditions associated with reduced immune resilience, including older age and HIV infection. Effective antiretroviral therapy increases CD4/CD8 T-cell ratios, but often not to preinfection levels. The reasons for this deficit remain unclear. As cytomegalovirus (CMV) infection exacerbates falling CD4/CD8 T-cell ratios and immune senescence in the old elderly population, we investigated whether CMV infection is associated with refractory inversion of CD4/CD8 T-cell ratios and increased phenotypic evidence of immune senescence in HIV infection. DESIG