Pub Date : 2021-01-01Epub Date: 2021-08-12DOI: 10.1007/s40610-021-00145-4
D L Kellogg, D L Kellogg, N Musi, A M Nambiar
Cellular senescence (CS) is increasingly implicated in the etiology of age-related diseases. While CS can facilitate physiological processes such as tissue repair and wound healing, senescent cells also contribute to pathophysiological processes involving macromolecular damage and metabolic dysregulation that characterize multiple morbid and prevalent diseases, including Alzheimer's disease, osteoarthritis, atherosclerotic vascular disease, diabetes mellitus, and idiopathic pulmonary fibrosis (IPF). Preclinical studies targeting senescent cells and the senescence-associated secretory phenotype (SASP) with "senotherapeutics" have demonstrated improvement in age-related morbidity associated with these disease states. Despite promising results from these preclinical trials, few human clinical trials have been conducted. A first-in-human, open-label, pilot study of the senolytic combination of dasatinib and quercetin (DQ) in patients with IPF showed improved physical function and mobility. In this review, we will discuss our current understanding of cellular senescence, its role in age-associated diseases, with a specific focus on IPF, and potential for senotherapeutics in the treatment of fibrotic lung diseases.
{"title":"Cellular Senescence in Idiopathic Pulmonary Fibrosis.","authors":"D L Kellogg, D L Kellogg, N Musi, A M Nambiar","doi":"10.1007/s40610-021-00145-4","DOIUrl":"10.1007/s40610-021-00145-4","url":null,"abstract":"<p><p>Cellular senescence (CS) is increasingly implicated in the etiology of age-related diseases. While CS can facilitate physiological processes such as tissue repair and wound healing, senescent cells also contribute to pathophysiological processes involving macromolecular damage and metabolic dysregulation that characterize multiple morbid and prevalent diseases, including Alzheimer's disease, osteoarthritis, atherosclerotic vascular disease, diabetes mellitus, and idiopathic pulmonary fibrosis (IPF). Preclinical studies targeting senescent cells and the senescence-associated secretory phenotype (SASP) with \"senotherapeutics\" have demonstrated improvement in age-related morbidity associated with these disease states. Despite promising results from these preclinical trials, few human clinical trials have been conducted. A first-in-human, open-label, pilot study of the senolytic combination of dasatinib and quercetin (DQ) in patients with IPF showed improved physical function and mobility. In this review, we will discuss our current understanding of cellular senescence, its role in age-associated diseases, with a specific focus on IPF, and potential for senotherapeutics in the treatment of fibrotic lung diseases.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"7 3","pages":"31-40"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39318061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01Epub Date: 2020-10-28DOI: 10.1007/s40610-020-00141-0
Yajun Liu, Qian Chen
Purpose of review: Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic application in tissue engineering and regenerative medicine. Despite their promise, recent findings suggest that MSC replication during repair process may lead to replicative senescence and stem cell exhaustion. Here, we review the basic mechanisms of MSC senescence, how it leads to degenerative diseases, and potential treatments for such diseases.
Recent findings: Emerging evidence has shown a link between senescent MSCs and degenerative diseases, especially age-related diseases such as osteoarthritis and idiopathic pulmonary fibrosis. During these disease processes, MSCs undergo cell senescence and mediate Senescence Associated Secretory Phenotypes (SASP) to affect the surrounding microenvironment. Thus, senescent MSCs can accelerate tissue aging by increasing the number of senescent cells and spreading inflammation to neighboring cells.
Summary: Senescent MSCs not only hamper tissue repair through cell senescence associated stem cell exhaustion, but also mediate tissue degeneration by initiating and spreading senescence-associated inflammation. It suggests new strategies of MSC-based cell therapy to remove, rejuvenate, or replace (3Rs) the senescent MSCs.
{"title":"Senescent Mesenchymal Stem Cells: Disease Mechanism and Treatment Strategy.","authors":"Yajun Liu, Qian Chen","doi":"10.1007/s40610-020-00141-0","DOIUrl":"10.1007/s40610-020-00141-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic application in tissue engineering and regenerative medicine. Despite their promise, recent findings suggest that MSC replication during repair process may lead to replicative senescence and stem cell exhaustion. Here, we review the basic mechanisms of MSC senescence, how it leads to degenerative diseases, and potential treatments for such diseases.</p><p><strong>Recent findings: </strong>Emerging evidence has shown a link between senescent MSCs and degenerative diseases, especially age-related diseases such as osteoarthritis and idiopathic pulmonary fibrosis. During these disease processes, MSCs undergo cell senescence and mediate Senescence Associated Secretory Phenotypes (SASP) to affect the surrounding microenvironment. Thus, senescent MSCs can accelerate tissue aging by increasing the number of senescent cells and spreading inflammation to neighboring cells.</p><p><strong>Summary: </strong>Senescent MSCs not only hamper tissue repair through cell senescence associated stem cell exhaustion, but also mediate tissue degeneration by initiating and spreading senescence-associated inflammation. It suggests new strategies of MSC-based cell therapy to remove, rejuvenate, or replace (3Rs) the senescent MSCs.</p>","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"6 4","pages":"173-182"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011589/pdf/nihms-1642077.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25558646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-01Epub Date: 2020-10-24DOI: 10.1007/s40610-020-00140-1
Iman M A Al-Naggar, George A Kuchel, Ming Xu
{"title":"Senolytics: targeting senescent cells for age-associated diseases.","authors":"Iman M A Al-Naggar, George A Kuchel, Ming Xu","doi":"10.1007/s40610-020-00140-1","DOIUrl":"https://doi.org/10.1007/s40610-020-00140-1","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"6 4","pages":"161-172"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-020-00140-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25525561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-08-18DOI: 10.1007/s40610-020-00139-8
H. Shankar, Shukla Saluja, Monica Rawat, Gyanendra Singh, M. Tarique, N. Mohammad, H. Naz
{"title":"The Causal Association Between Occupational, Environmental, and Lifestyle Factors and Reproductive Cancer Risk","authors":"H. Shankar, Shukla Saluja, Monica Rawat, Gyanendra Singh, M. Tarique, N. Mohammad, H. Naz","doi":"10.1007/s40610-020-00139-8","DOIUrl":"https://doi.org/10.1007/s40610-020-00139-8","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"6 1","pages":"149 - 160"},"PeriodicalIF":0.0,"publicationDate":"2020-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-020-00139-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42778912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-07-15DOI: 10.1007/s40610-020-00138-9
H. Naz, M. Tarique, M. Suhail, H. Shankar, Naoshad Muhammad, Darksha Usmani, M. Ashraf, T. Zughaibi
{"title":"Calcium-/Calmodulin-Dependent Protein Kinase IV (CAMKIV): A Multifunctional Enzyme and Its Role in Various Cancer: An Update","authors":"H. Naz, M. Tarique, M. Suhail, H. Shankar, Naoshad Muhammad, Darksha Usmani, M. Ashraf, T. Zughaibi","doi":"10.1007/s40610-020-00138-9","DOIUrl":"https://doi.org/10.1007/s40610-020-00138-9","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"6 1","pages":"139 - 147"},"PeriodicalIF":0.0,"publicationDate":"2020-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-020-00138-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42955444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-17DOI: 10.1007/s40610-020-00137-w
Ekansh Mittal, S. Deore, Mahendra Kumar, M. Krishnasastry
{"title":"When to Die Is the Question: Need and Manipulation of Cell Death by Mycobacterium","authors":"Ekansh Mittal, S. Deore, Mahendra Kumar, M. Krishnasastry","doi":"10.1007/s40610-020-00137-w","DOIUrl":"https://doi.org/10.1007/s40610-020-00137-w","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"6 1","pages":"103 - 115"},"PeriodicalIF":0.0,"publicationDate":"2020-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-020-00137-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41640905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-01DOI: 10.1007/s40610-020-00132-1
J. Ziermann
{"title":"Developmental Correlations of Head and Heart Musculature: Importance for Understanding Human Syndromes","authors":"J. Ziermann","doi":"10.1007/s40610-020-00132-1","DOIUrl":"https://doi.org/10.1007/s40610-020-00132-1","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"6 1","pages":"62-70"},"PeriodicalIF":0.0,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-020-00132-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41407618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-23DOI: 10.1007/s40610-020-00129-w
Sadaf, Mohammad Z Najm, V. Shingatgeri, M. Uddin, M. Izhari, M. Akhtar, A. Kathait, S. Kar, Ishita Jain, Pulkit Datt, K. Komal, Anoushka Sharma
{"title":"The Pivotal Role of Senescence in Cell Death and Aging: Where Do We Stand?","authors":"Sadaf, Mohammad Z Najm, V. Shingatgeri, M. Uddin, M. Izhari, M. Akhtar, A. Kathait, S. Kar, Ishita Jain, Pulkit Datt, K. Komal, Anoushka Sharma","doi":"10.1007/s40610-020-00129-w","DOIUrl":"https://doi.org/10.1007/s40610-020-00129-w","url":null,"abstract":"","PeriodicalId":72737,"journal":{"name":"Current molecular biology reports","volume":"6 1","pages":"91-101"},"PeriodicalIF":0.0,"publicationDate":"2020-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s40610-020-00129-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47409094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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