Cellular Senescence: Molecular Targets, Biomarkers, and Senolytic Drugs

被引:85
作者
Kudlova, Natalie [1 ]
De Sanctis, Juan Bautista [1 ,2 ]
Hajduch, Marian [1 ,2 ]
机构
[1] Palacky Univ, Inst Mol & Translat Med, Fac Med & Dent, Olomouc 77147, Czech Republic
[2] Palacky Univ, Inst Mol & Translat Med, Czech Adv Technol & Res Inst, Olomouc 77147, Czech Republic
关键词
senescence; aging; cellular model; mouse model; senolytics; BREAST-CANCER CELLS; DNA-DAMAGE; SECRETORY PHENOTYPE; D-GALACTOSE; IN-VIVO; OXIDATIVE STRESS; COGNITIVE IMPAIRMENT; TRANSCRIPTION FACTOR; SELECTIVE INHIBITOR; BETA-GALACTOSIDASE;
D O I
10.3390/ijms23084168
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cellular senescence is defined as irreversible cell cycle arrest caused by various processes that render viable cells non-functional, hampering normal tissue homeostasis. It has many endogenous and exogenous inducers, and is closely connected with age, age-related pathologies, DNA damage, degenerative disorders, tumor suppression and activation, wound healing, and tissue repair. However, the literature is replete with contradictory findings concerning its triggering mechanisms, specific biomarkers, and detection protocols. This may be partly due to the wide range of cellular and in vivo animal or human models of accelerated aging that have been used to study senescence and test senolytic drugs. This review summarizes recent findings concerning senescence, presents some widely used cellular and animal senescence models, and briefly describes the best-known senolytic agents.
引用
收藏
页数:26
相关论文
共 218 条
[1]   Chemokine signaling via the CXCR2 receptor reinforces senescence [J].
Acosta, Juan C. ;
O'Loghlen, Ana ;
Banito, Ana ;
Guijarro, Maria V. ;
Augert, Arnaud ;
Raguz, Selina ;
Fumagalli, Marzia ;
Da Costa, Marco ;
Brown, Celia ;
Popov, Nikolay ;
Takatsu, Yoshihiro ;
Melamed, Jonathan ;
di Fagagna, Fabrizio d'Adda ;
Bernard, David ;
Hernando, Eva ;
Gil, Jesus .
CELL, 2008, 133 (06) :1006-1018
[2]   Healing and Hurting: Molecular Mechanisms, Functions, and Pathologies of Cellular Senescence [J].
Adams, Peter D. .
MOLECULAR CELL, 2009, 36 (01) :2-14
[3]   Multiparameter flow cytometric detection and quantification of senescent cellsin vitro [J].
Adewoye, Adeolu Badi ;
Tampakis, Dimitris ;
Follenzi, Antonia ;
Stolzing, Alexandra .
BIOGERONTOLOGY, 2020, 21 (06) :773-786
[4]   Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles [J].
Agostini, Alessandro ;
Mondragon, Laura ;
Bernardos, Andrea ;
Martinez-Manez, Ramon ;
Dolores Marcos, M. ;
Sancenon, Felix ;
Soto, Juan ;
Costero, Ana ;
Manguan-Garcia, Cristina ;
Perona, Rosario ;
Moreno-Torres, Marta ;
Aparicio-Sanchis, Rafael ;
Ramon Murguia, Jose .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (42) :10556-10560
[5]   Differential Regulation of Methylation-Regulating Enzymes by Senescent Stromal Cells Drives Colorectal Cancer Cell Response to DNA-Demethylating Epi-Drugs [J].
Agrawal, Khushboo ;
Das, Viswanath ;
Taborska, Natalie ;
Gursky, Jan ;
Dzubak, Petr ;
Hajduch, Marian .
STEM CELLS INTERNATIONAL, 2018, 2018
[6]  
Aird Katherine M, 2013, Methods Mol Biol, V965, P185, DOI 10.1007/978-1-62703-239-1_12
[7]   The Role of the Cyclin Dependent Kinase Inhibitor p21cip1/waf1 in Targeting Cancer: Molecular Mechanisms and Novel Therapeutics [J].
Al Bitar, Samar ;
Gali-Muhtasib, Hala .
CANCERS, 2019, 11 (10)
[8]   Suppression of the senescence-associated secretory phenotype (SASP) in human fibroblasts using small molecule inhibitors of p38 MAP kinase and MK2 [J].
Alimbetov, Dauren ;
Davis, Terence ;
Brook, Amy J. C. ;
Cox, Lynne S. ;
Faragher, Richard G. A. ;
Nurgozhin, Talgat ;
Zhumadilov, Zhaxybay ;
Kipling, David .
BIOGERONTOLOGY, 2016, 17 (02) :305-315
[9]   Characterization of novel markers of senescence and their prognostic potential in cancer [J].
Althubiti, M. ;
Lezina, L. ;
Carrera, S. ;
Jukes-Jones, R. ;
Giblett, S. M. ;
Antonov, A. ;
Barlev, N. ;
Saldanha, G. S. ;
Pritchard, C. A. ;
Cain, K. ;
Macip, S. .
CELL DEATH & DISEASE, 2014, 5 :e1528-e1528
[10]   Senolytic CAR T cells reverse senescence-associated pathologies [J].
Amor, Corina ;
Feucht, Judith ;
Leibold, Josef ;
Ho, Yu-Jui ;
Zhu, Changyu ;
Alonso-Curbelo, Direna ;
Mansilla-Soto, Jorge ;
Boyer, Jacob A. ;
Li, Xiang ;
Giavridis, Theodoros ;
Kulick, Amanda ;
Houlihan, Shauna ;
Peerschke, Ellinor ;
Friedman, Scott L. ;
Ponomarev, Vladimir ;
Piersigilli, Alessandra ;
Sadelain, Michel ;
Lowe, Scott W. .
NATURE, 2020, 583 (7814) :127-+