Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy DOI Creative Commons
Pataje G.S. Prasanna, Deborah E. Citrin,

Jeffrey Hildesheim

et al.

JNCI Journal of the National Cancer Institute, Journal Year: 2021, Volume and Issue: 113(10), P. 1285 - 1298

Published: March 31, 2021

Cellular senescence is an essential tumor suppressive mechanism that prevents the propagation of oncogenically activated, genetically unstable, and/or damaged cells. Induction cell also one underlying mechanisms by which cancer therapies exert antitumor activity. However, increasing body evidence from preclinical studies demonstrates radiation and chemotherapy cause accumulation senescent cells (SnCs) both in normal tissue. SnCs tumors can, paradoxically, promote relapse, metastasis, resistance to therapy, part, through expression senescence-associated secretory phenotype. In addition, tissue can contribute certain radiation- chemotherapy-induced side effects. Because its multiple roles, cellular could serve as important target fight against cancer. This commentary provides a summary discussion at National Cancer Institute Workshop on Radiation, Senescence, (August 10-11, 2020, Institute, Bethesda, MD) regarding current status research, heterogeneity therapy-induced senescence, senotherapeutics molecular biomarkers, concept "one-two punch" therapy (consisting therapeutics induce followed selective clearance SnCs), integration with personalized adaptive therapy. It identifies key knowledge gaps outlines future directions this emerging field improve treatment outcomes for patients.

Language: Английский

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

486
Mechanisms and therapeutic implications of cellular senescence in osteoarthritis DOI
Philip Coryell, Brian O. Diekman, Richard F. Loeser

et al.

Nature Reviews Rheumatology, Journal Year: 2020, Volume and Issue: 17(1), P. 47 - 57

Published: Nov. 18, 2020

Language: Английский

Citations

473
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

442
A guide to assessing cellular senescencein vitroandin vivo DOI Creative Commons
Estela González‐Gualda, Andrew Baker, Ljiljana Fruk

et al.

FEBS Journal, Journal Year: 2020, Volume and Issue: 288(1), P. 56 - 80

Published: Sept. 22, 2020

Cellular senescence is a physiological mechanism whereby proliferating cell undergoes stable cycle arrest upon damage or stress and elicits secretory phenotype. This highly dynamic regulated cellular state plays beneficial roles in physiology, such as during embryonic development wound healing, but it can also result antagonistic effects age-related pathologies, degenerative disorders, ageing cancer. In an effort to better identify this complex state, given that universal marker has yet be identified, general set of hallmarks describing been established. However, the senescent programme becomes more defined, further complexities, including phenotype heterogeneity, have emerged. significantly complicates recognition evaluation senescence, especially within tissues living organisms. To address these challenges, substantial efforts are currently being made towards discovery novel specific biomarkers, optimized combinatorial strategies emerging detection techniques. Here, we compile advances present multifactorial guide assess cultures, The reliable assessment identification not only crucial for understanding its underlying biology, imperative diagnostic therapeutic aimed at targeting clinic.

Language: Английский

Citations

424
Immune cell-mediated features of non-alcoholic steatohepatitis DOI Creative Commons
Thierry Huby, Emmanuel L. Gautier

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 429 - 443

Published: Nov. 5, 2021

Non-alcoholic fatty liver disease (NAFLD) includes a range of hepatic manifestations, starting with steatosis and potentially evolving towards non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma. NAFLD is major health burden, its incidence increasing worldwide. Although it primarily disturbed metabolism, involves several immune cell-mediated inflammatory processes, particularly when reaching the stage NASH, at which point inflammation becomes integral to progression disease. The cell landscape diverse steady state further evolves during NASH direct consequences for severity. In this Review, we discuss current concepts related role cells in onset NASH. A better understanding mechanisms by contribute pathogenesis should aid design innovative drugs target therapeutic options are limited. (NASH) serious chronic disorder prevalence Metabolic nature, also mobilizes system. Here, Huby Gautier knowledge regarding how subsets affect progression.

Language: Английский

Citations

382
Strategies for targeting senescent cells in human disease DOI Open Access
Nathan Gasek, George A. Kuchel, James L. Kirkland

et al.

Nature Aging, Journal Year: 2021, Volume and Issue: 1(10), P. 870 - 879

Published: Oct. 7, 2021

Language: Английский

Citations

342
CAR immune cells: design principles, resistance and the next generation DOI
Louai Labanieh, Crystal L. Mackall

Nature, Journal Year: 2023, Volume and Issue: 614(7949), P. 635 - 648

Published: Feb. 22, 2023

Language: Английский

Citations

338
Immunosenescence: a key player in cancer development DOI Creative Commons
Jingyao Lian, Ying Yue,

Weina Yu

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Nov. 10, 2020

Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling lymphoid organs, leading to changes in the function elderly, which closely related development infections, autoimmune diseases, malignant tumors. T cell-output decline an important feature immunosenescence as well production senescence-associated secretory phenotype, increased glycolysis, reactive oxygen species. Senescent cells exhibit abnormal phenotypes, including downregulation CD27, CD28, upregulation CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, cytotoxic T-lymphocyte-associated protein 4, are tightly The role tumors sophisticated: many factors involved include cAMP, glucose competition, oncogenic stress tumor microenvironment, can induce senescence cells, macrophages, natural dendritic cells. Accordingly, these senescent could also affect progression. In addition, effect on response checkpoint blocking antibody therapy so far ambiguous due low participation elderly cancer patients clinical trials. Furthermore, other senescence-related interventions be possible genetic pharmacological methods, mTOR inhibition, interleukin-7 recombination, NAD+ activation. Overall, this review aims highlight characteristics its impact immunotherapy, especially future directions treatment through senescence-focused strategies.

Language: Английский

Citations

331
Immunosenescence: molecular mechanisms and diseases DOI Creative Commons

Zaoqu Liu,

Qimeng Liang,

Yuqing Ren

et al.

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

Citations

319
Cellular senescence: a key therapeutic target in aging and diseases DOI Creative Commons
Lei Zhang,

Louise E. Pitcher,

Matthew J. Yousefzadeh

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(15)

Published: July 31, 2022

Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary disrupts tissue homeostasis, resulting loss repair regeneration. The use transgenic mouse models which SnCs be genetically ablated has established key role for driving age-related disease. Importantly, senotherapeutics have been developed pharmacologically eliminate SnCs, termed senolytics, or suppress SASP other markers senescence, senomorphics. Based on extensive preclinical studies as well small clinical trials demonstrating benefits senotherapeutics, multiple are under way. This Review discusses diseases, strategies target approaches discover advances senolytics.

Language: Английский

Citations

311