Cellular senescence and the senescent secretory phenotype: therapeutic opportunities.
TLDR
This work reviews the mechanisms that induce senescence and the SASP, their associations with chronic disease and frailty, therapeutic opportunities based on targeting senescent cells and the ASP, and potential paths to developing clinical interventions.Abstract:
Aging is the largest risk factor for most chronic diseases, which account for the majority of morbidity and health care expenditures in developed nations. New findings suggest that aging is a modifiable risk factor, and it may be feasible to delay age-related diseases as a group by modulating fundamental aging mechanisms. One such mechanism is cellular senescence, which can cause chronic inflammation through the senescence-associated secretory phenotype (SASP). We review the mechanisms that induce senescence and the SASP, their associations with chronic disease and frailty, therapeutic opportunities based on targeting senescent cells and the SASP, and potential paths to developing clinical interventions.read more
Citations
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Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
TL;DR: The session on inflammation of the Advances in Gerosciences meeting held at the National Institutes of Health/National Institute on Aging in Bethesda on October 30 and 31, 2013 was aimed at defining these important unanswered questions about inflammaging.
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Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
TL;DR: Coppe et al. as mentioned in this paper showed that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy, including interleukin (IL)-6 and IL-8.
Journal ArticleDOI
The role of senescent cells in ageing
TL;DR: A deeper understanding of the molecular mechanisms underlying the multi-step progression of senescence and the development and function of acute versus chronic senescent cells may lead to new therapeutic strategies for age-related pathologies and extend healthy lifespan.
Journal ArticleDOI
The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs
Yi-Yi Zhu,Tamara Tchkonia,Tamar Pirtskhalava,Adam C. Gower,Husheng Ding,Nino Giorgadze,Allyson K. Palmer,Yuji Ikeno,Yuji Ikeno,Gene B. Hubbard,Gene B. Hubbard,Marc E. Lenburg,Steven P. O'Hara,Nicholas F. LaRusso,Jordan D. Miller,Carolyn M Roos,Grace C Verzosa,Nathan K. LeBrasseur,Jonathan D. Wren,Joshua N. Farr,Sundeep Khosla,Michael B. Stout,Sara J. McGowan,Heike Fuhrmann-Stroissnigg,Aditi U. Gurkar,Jing-jing Zhao,Debora Colangelo,Akaitz Dorronsoro,Yuan Yuan Ling,Amira S. Barghouthy,Diana C. Navarro,Tokio Sano,Paul D. Robbins,Laura J. Niedernhofer,James L. Kirkland +34 more
TL;DR: The results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.
Journal ArticleDOI
Senolytics improve physical function and increase lifespan in old age
Ming Xu,Ming Xu,Tamar Pirtskhalava,Joshua N. Farr,Bettina M. Weigand,Bettina M. Weigand,Allyson K. Palmer,Megan M. Weivoda,Christina L. Inman,Mikolaj Ogrodnik,Mikolaj Ogrodnik,Christine M Hachfeld,Daniel G. Fraser,Jennifer L Onken,Kurt O. Johnson,Grace C Verzosa,Larissa G.P. Langhi,Moritz Weigl,Nino Giorgadze,Nathan K. LeBrasseur,Jordan D. Miller,Diana Jurk,Ravinder J. Singh,David B. Allison,David B. Allison,Keisuke Ejima,Keisuke Ejima,Gene B. Hubbard,Yuji Ikeno,Yuji Ikeno,Hajrunisa Cubro,Vesna D. Garovic,Xiaonan Hou,S. John Weroha,Paul D. Robbins,Laura J. Niedernhofer,Sundeep Khosla,Tamara Tchkonia,James L. Kirkland +38 more
TL;DR: It is demonstrated that transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues, and a senolytic can reverse this dysfunction and potently increase lifespan in aged mice.
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