TNF‐α/IFN‐γ synergy amplifies senescence‐associated inflammation and SARS‐CoV‐2 receptor expression via hyper‐activated JAK/STAT1 DOI
Renuka Kandhaya‐Pillai, Xiaomeng Yang, Tamar Tchkonia

et al.

Aging Cell, Journal Year: 2022, Volume and Issue: 21(6)

Published: May 30, 2022

Abstract Older age and underlying conditions such as diabetes/obesity or immunosuppression are leading host risk factors for developing severe complications from COVID‐19 infection. The pathogenesis of COVID‐19‐related cytokine storm, tissue damage, fibrosis may be interconnected with fundamental aging processes, including dysregulated immune responses cellular senescence. Here, we examined effects key cytokines linked to senescence on expression SARS‐CoV‐2 viral entry receptors. We found exposure human umbilical vein endothelial cells (HUVECs) the inflammatory cytokines, TNF‐α + IFN‐γ a cocktail IL‐6, increased ACE2/DPP4, accentuated pro‐inflammatory senescence‐associated secretory phenotype (SASP), decreased proliferative capacity, consistent progression towards senescence‐like state. IL‐6 by itself failed induce substantial receptors SASP‐related genes, while synergy between initiated positive feedback loop via hyper‐activation JAK/STAT1 pathway, causing SASP amplification. Breaking interactive secretion JAK inhibitor ruxolitinib antiviral drug remdesivir prevented hyper‐inflammation, normalized receptor expression, restored HUVECs capacity. This appears underlie cytokine‐mediated activation links hyper‐inflammation.

Language: Английский

Cellular senescence and senolytics: the path to the clinic DOI Open Access
Selim Chaib, Tamar Tchkonia, James L. Kirkland

et al.

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(8), P. 1556 - 1568

Published: Aug. 1, 2022

Language: Английский

Citations

626

Exploiting senescence for the treatment of cancer DOI Open Access
Liqin Wang, Lina Lankhorst, René Bernards

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(6), P. 340 - 355

Published: March 3, 2022

Language: Английский

Citations

513

Inflammation and aging: signaling pathways and intervention therapies DOI Creative Commons
Xia Li, Chentao Li, Wanying Zhang

et al.

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

Citations

474

Senescence and cancer — role and therapeutic opportunities DOI Open Access
Clemens A. Schmitt, Boshi Wang, Marco Demaria

et al.

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(10), P. 619 - 636

Published: Aug. 31, 2022

Language: Английский

Citations

439

Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies DOI Open Access
Suowen Xu, Iqra Ilyas, Jianping Weng

et al.

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 44(4), P. 695 - 709

Published: Oct. 17, 2022

Language: Английский

Citations

278

Mechanisms and Regulation of Cellular Senescence DOI Open Access

Lauréline Roger,

Fanny Tomas,

Véronique Gire

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 13173 - 13173

Published: Dec. 6, 2021

Cellular senescence entails a state of an essentially irreversible proliferative arrest in which cells remain metabolically active and secrete range pro-inflammatory proteolytic factors as part the senescence-associated secretory phenotype. There are different types senescent cells, can be induced response to many DNA damage signals. Senescent accumulate tissues organs where they have distinct physiological pathological functions. Despite this diversity, all must able survive nondividing while protecting themselves from positive feedback loops linked constant activation response. This capacity requires changes core cellular programs. Understanding how cell undergo extensive their transcriptional programs, metabolism, heterochromatin patterns, structures induce common is crucial preventing cancer development/progression improving health during aging. In review, we discuss continuously evolve after initial highlight unifying features that define state.

Language: Английский

Citations

222

Skin Aging, Cellular Senescence and Natural Polyphenols DOI Open Access

Erika Csekes,

Lucia Račková

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 12641 - 12641

Published: Nov. 23, 2021

The skin, being the barrier organ of body, is constitutively exposed to various stimuli impacting its morphology and function. Senescent cells have been found accumulate with age may contribute age-related skin changes pathologies. Natural polyphenols exert many health benefits, including ameliorative effects on aging. By affecting molecular pathways senescence, are able prevent or delay senescence formation and, consequently, avoid ameliorate aging age-associated pathologies skin. This review aims provide an overview current state knowledge in cellular summarize recent vitro studies related anti-senescent mechanisms natural carried out keratinocytes, melanocytes fibroblasts. Aged context COVID-19 pandemic will be also discussed.

Language: Английский

Citations

190

Cytoplasmic DNA: sources, sensing, and role in aging and disease DOI
Karl N. Miller, Stella Victorelli, Hanna Salmonowicz

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(22), P. 5506 - 5526

Published: Oct. 1, 2021

Language: Английский

Citations

184

A single-cell transcriptomic landscape of the lungs of patients with COVID-19 DOI Open Access
Si Wang, Xiaohong Yao, Shuai Ma

et al.

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(12), P. 1314 - 1328

Published: Dec. 1, 2021

Language: Английский

Citations

162

Interconnections between Inflammageing and Immunosenescence during Ageing DOI Creative Commons
Thibault Teissier, Éric Boulanger, Lynne S. Cox

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 359 - 359

Published: Jan. 21, 2022

Acute inflammation is a physiological response to injury or infection, with cascade of steps that ultimately lead the recruitment immune cells clear invading pathogens and heal wounds. However, chronic arising from continued presence initial trigger, dysfunction signalling and/or effector pathways, harmful health. While successful ageing in older adults, including centenarians, associated low levels inflammation, elevated increases risk poor health death. Hence has been described as one seven pillars ageing. Age-associated sterile, chronic, low-grade commonly termed inflammageing-it not simply consequence increasing chronological age, but also marker biological ageing, multimorbidity, mortality risk. inflammageing was initially thought be caused by "continuous antigenic load stress", reports last two decades describe much more complex phenomenon involving cellular senescence system. In this review, we explore some main sources consequences context immunosenescence highlight potential interventions. particular, assess contribution age-associated identify patterns pro- anti-inflammatory markers characteristic inflammageing, alterations system finally ways diet, exercise, pharmacological interventions can reduce thus, improve later life

Language: Английский

Citations

162