Aging and chronic inflammation: highlights from a multidisciplinary workshop

Immunity & Ageing, Год журнала: 2023, Номер 20(1)

Опубликована: Июнь 8, 2023

Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. entails the immune system characterized by decrease thymic output naïve lymphocytes, an accumulated chronic antigenic stress notably caused infections such as cytomegalovirus (CMV), cell senescence with acquisition inflammatory senescence-associated secretory phenotype (SASP). For this reason, due to SASP originating from other tissues, aging commonly accompanied low-grade inflammation, termed "inflammaging". After decades accumulating evidence regarding age-related processes domain now appears mature enough allow integrative reinterpretation old data. Here, we provide overview topics discussed recent workshop "Aging Chronic Inflammation" which many major players field contributed. We highlight advances systematic measurement interpretation biological markers aging, well their implications for human health longevity interventions that can be envisaged maintain or improve function older people.

Язык: Английский

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Targeting senescent cells for a healthier longevity: the roadmap for an era of global aging

Life Medicine, Год журнала: 2022, Номер 1(2), С. 103 - 119

Опубликована: Авг. 9, 2022

Abstract Aging is a natural but relentless process of physiological decline, leading to physical frailty, reduced ability respond stresses (resilience) and, ultimately, organismal death. Cellular senescence, self-defensive mechanism activated in response intrinsic stimuli and/or exogenous stress, one the central hallmarks aging. Senescent cells cease proliferate, while remaining metabolically active and secreting numerous extracellular factors, feature known as senescence-associated secretory phenotype. Senescence physiologically important for embryonic development, tissue repair, wound healing, prevents carcinogenesis. However, chronic accumulation persisting senescent contributes host pathologies including age-related morbidities. By paracrine endocrine mechanisms, can induce inflammation locally systemically, thereby causing dysfunction, organ degeneration. Agents those targeting damaging components phenotype or inducing apoptosis exhibit remarkable benefits both preclinical models early clinical trials geriatric conditions. Here we summarize features outline strategies holding potential be developed interventions. In long run, there an increasing demand safe, effective, clinically translatable senotherapeutics address healthcare needs current settings global

Язык: Английский

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Pulmonary infection by SARS-CoV-2 induces senescence accompanied by an inflammatory phenotype in severe COVID-19: possible implications for viral mutagenesis

European Respiratory Journal, Год журнала: 2022, Номер 60(2), С. 2102951 - 2102951

Опубликована: Янв. 27, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the system can progress to a multisystemic disease with aberrant inflammatory response. Cellular senescence promotes chronic inflammation, named senescence-associated secretory phenotype (SASP). We investigated whether 2019 (COVID-19) is associated cellular and SASP.Autopsy lung tissue samples from 11 COVID-19 patients 43 age-matched non-COVID-19 controls similar comorbidities were analysed by immunohistochemistry for SARS-CoV-2, markers key SASP cytokines. Virally induced was functionally recapitulated in vitro, infecting epithelial Vero-E6 cells three-dimensional alveosphere alveolar type (AT2) SARS-CoV-2 strains isolated patients.SARS-CoV-2 detected immunocytochemistry electron microscopy predominantly AT2 cells. Infected expressed angiotensin-converting enzyme exhibited increased (p16INK4A SenTraGor positivity) interleukin (IL)-1β IL-6 expression. In (SenTraGor), DNA damage (γ-H2AX) cytokine (IL-1β, IL-6, CXCL8) apolipoprotein B mRNA-editing (APOBEC) Next-generation sequencing analysis progenies obtained infected/senescent demonstrated APOBEC-mediated mutations. Dissemination SARS-CoV-2-infection confirmed extrapulmonary sites (kidney liver) patient.We demonstrate that severe COVID-19, infected exhibit proinflammatory phenotype. induces inflammation. Importantly, senescent may act as source mutagenesis mediated APOBEC enzymes. Therefore, SARS-CoV-2-induced be an important molecular mechanism persistence mutagenesis.

Язык: Английский

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Stress, epigenetics, and aging: Unraveling the intricate crosstalk

Molecular Cell, Год журнала: 2023, Номер 84(1), С. 34 - 54

Опубликована: Ноя. 13, 2023

Язык: Английский

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Senescent Cells: A Therapeutic Target in Cardiovascular Diseases

Cells, Год журнала: 2023, Номер 12(9), С. 1296 - 1296

Опубликована: Май 2, 2023

Senescent cell accumulation has been observed in age-associated diseases including cardiovascular diseases. cells lack proliferative capacity and secrete senescence-associated secretory phenotype (SASP) factors that may cause or worsen many Therapies targeting senescent cells, especially senolytic drugs selectively induce removal, have shown to delay, prevent, alleviate, treat multiple preclinical models. Some clinical trials already completed are underway for a number of geriatric syndromes. Understanding how cellular senescence affects the various types system, such as endothelial vascular smooth muscle fibroblasts, immune progenitor cardiomyocytes, is important facilitate translation senotherapeutics into interventions. This review highlights: (1) characteristics their involvement diseases, focusing on aforementioned types, (2) evidence about other senotherapeutics, (3) future path potential

Язык: Английский

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