Hallmarks of aging: An expanding universe

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 243 - 278

Published: Jan. 1, 2023

Language: Английский

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Inflammation and aging: signaling pathways and intervention therapies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 8, 2023

Abstract Aging is characterized by systemic chronic inflammation, which accompanied cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there an urgent need for a systematic organization inflammaging through dimensionality reduction. Factors secreted senescent cells, known as senescence-associated secretory phenotype (SASP), promote inflammation can induce senescence in normal cells. At same time, accelerates immune resulting weakened function inability to clear cells inflammatory factors, creates vicious cycle senescence. Persistently elevated levels organs such bone marrow, liver, lungs cannot be eliminated leading damage aging-related Therefore, has been recognized endogenous factor elimination could potential strategy anti-aging. Here we discuss at molecular, cellular, organ, disease levels, review current aging models, implications cutting-edge single cell technologies, well anti-aging strategies. Since preventing alleviating diseases improving overall quality life are ultimate goals research, our highlights critical features mechanisms along with latest developments future directions providing theoretical foundation novel practical

Language: Английский

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Hallmarks of T cell aging

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(6), P. 687 - 698

Published: May 13, 2021

Language: Английский

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Immunosenescence: molecular mechanisms and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 13, 2023

Abstract Infection susceptibility, poor vaccination efficacy, age-related disease onset, and neoplasms are linked to innate adaptive immune dysfunction that accompanies aging (known as immunosenescence). During aging, organisms tend develop a characteristic inflammatory state expresses high levels of pro-inflammatory markers, termed inflammaging. This chronic inflammation is typical phenomenon immunosenescence it considered the major risk factor for diseases. Thymic involution, naïve/memory cell ratio imbalance, dysregulated metabolism, epigenetic alterations striking features immunosenescence. Disturbed T-cell pools antigen stimulation mediate premature senescence cells, senescent cells proinflammatory senescence-associated secretory phenotype exacerbates Although underlying molecular mechanisms remain be addressed, well documented T inflammaging might driving forces in Potential counteractive measures will discussed, including intervention cellular metabolic-epigenetic axes mitigate In recent years, has attracted increasing attention its role tumor development. As result limited participation elderly patients, impact on cancer immunotherapy unclear. Despite some surprising results from clinical trials drugs, necessary investigate other

Language: Английский

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Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders

Science, Journal Year: 2021, Volume and Issue: 373(6553)

Published: June 3, 2021

The meninges contain adaptive immune cells that provide immunosurveillance of the central nervous system (CNS). These are thought to derive from systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show meningeal B locally calvaria, which harbors a niche for hematopoiesis. reach calvaria through specialized vascular connections. This calvarial-meningeal path cell development may CNS with constant supply educated by antigens. Conversely, subset antigen-experienced populate in aging mice blood-borne. results identify private source cells, help maintain privilege within CNS.

Language: Английский

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Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children

Nature Biotechnology, Journal Year: 2021, Volume and Issue: 40(3), P. 319 - 324

Published: Aug. 18, 2021

Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize single-cell transcriptional landscape upper airways of SARS-CoV-2-negative (n = 18) age-matched SARS-CoV-2-positive 24) children corresponding samples from adults 44), covering an range 4 weeks to 77 years. displayed higher basal expression relevant pattern recognition receptors such as MDA5 (IFIH1) RIG-I (DDX58) airway epithelial cells, macrophages dendritic resulting stronger innate antiviral responses upon SARS-CoV-2 than We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)+ cytotoxic T cells CD8+ population memory phenotype occurring predominantly children. Our study provides evidence that are primed virus sensing, early response Single-cell sequencing reveals pre-activated immunity important milder COVID-19 symptoms

Language: Английский

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Cytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox

Immunity, Journal Year: 2021, Volume and Issue: 54(12), P. 2701 - 2711

Published: Dec. 1, 2021

Cytotoxic T cells are important effectors of anti-tumor immunity. While tumor killing is ascribed to CD8+ cell function, pre-clinical and clinical studies have identified intra-tumoral CD4+ that possess cytotoxic programs can directly kill cancer cells. found in other disease settings including infection autoimmunity. Here, we review the phenotypic functional characteristics non-cancer contexts. We conduct a comparative examination cytolytic mechanisms across states synthesize features define these independent context. discuss regulatory driving ontogeny effector function evidence for relevance cancer. In this context, highlight gaps understanding biology as well potential use immunotherapies specific cancers.

Language: Английский

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Immune ageing at single-cell resolution

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(8), P. 484 - 498

Published: Nov. 23, 2021

Language: Английский

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Ageing and rejuvenation of tissue stem cells and their niches

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(1), P. 45 - 62

Published: July 20, 2022

Language: Английский

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Biomarkers of aging

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

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