Senopathies-Diseases Associated with Cellular Senescence

被引:14
作者
Lushchak, Oleh [1 ,2 ,3 ]
Schosserer, Markus [4 ,5 ]
Grillari, Johannes [1 ,5 ,6 ]
机构
[1] Ludwig Boltzmann Inst Traumatol, Res Ctr Cooperat AUVA, A-1200 Vienna, Austria
[2] Precarpathian Natl Univ, Dept Biochem & Biotechnol, UA-76000 Ivano Frankivsk, Ukraine
[3] Res & Dev Univ, UA-76018 Ivano Frankivsk, Ukraine
[4] Med Univ Vienna, Inst Med Genet, Ctr Pathobiochem & Genet, A-1090 Vienna, Austria
[5] Austrian Cluster Tissue Regenerat, A-1200 Vienna, Austria
[6] Univ Nat Resources & Life Sci, Inst Mol Biotechnol, Dept Biotechnol, A-1190 Vienna, Austria
基金
奥地利科学基金会;
关键词
cellular senescence; aging; senopathy; senolytic; senomorphic; senotherapy; geroscience; senescence-associated secretory phenotype (SASP); pathology; age-related disease; SECRETORY PHENOTYPE; CELLS; FIBROSIS; MECHANISMS; CLEARANCE; METFORMIN; SHORTEN; CANCER; SASP;
D O I
10.3390/biom13060966
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 describes a stable cell cycle arrest state with a characteristic phenotype. Senescent cells accumulate in the human body during normal aging, limiting the lifespan and promoting aging-related, but also several non-related, pathologies. We propose to refer to all diseases whose pathogenesis or progression is associated with cellular senescence as "senopathies". Targeting senescent cells with senolytics or senomorphics is likely to mitigate these pathologies. Examples of senopathies include cardiovascular, metabolic, musculoskeletal, liver, kidney, and lung diseases and neurodegeneration. For all these pathologies, animal studies provide clear mechanistic evidence for a connection between senescent cell accumulation and disease progression. The major persisting challenge in developing novel senotherapies is the heterogeneity of senescence phenotypes, causing a lack of universal biomarkers and difficulties in discriminating senescent from non-senescent cells.
引用
收藏
页数:10
相关论文
共 84 条
[1]  
Aird Katherine M, 2013, Methods Mol Biol, V965, P185, DOI 10.1007/978-1-62703-239-1_12
[2]   Senolytics: Targeting Senescent Cells for Age-Associated Diseases [J].
Iman M. A. Al-Naggar ;
George A. Kuchel ;
Ming Xu .
Current Molecular Biology Reports, 2020, 6 (4) :161-172
[3]   Length-independent telomere damage drives post-mitotic cardiomyocyte senescence [J].
Anderson, Rhys ;
Lagnado, Anthony ;
Maggiorani, Damien ;
Walaszczyk, Anna ;
Dookun, Emily ;
Chapman, James ;
Birch, Jodie ;
Salmonowicz, Hanna ;
Ogrodnik, Mikolaj ;
Jurk, Diana ;
Proctor, Carole ;
Correia-Melo, Clara ;
Victorelli, Stella ;
Fielder, Edward ;
Berlinguer-Palmini, Rolando ;
Owens, Andrew ;
Greaves, Laura C. ;
Kolsky, Kathy L. ;
Parini, Angelo ;
Douin-Echinard, Victorine ;
Lebrasseur, Nathan K. ;
Arthur, Helen M. ;
Tual-Chalot, Simon ;
Schafer, Marissa J. ;
Roos, Carolyn M. ;
Miller, Jordan D. ;
Robertson, Neil ;
Mann, Jelena ;
Adams, Peter D. ;
Tchkonia, Tamara ;
Kirkland, James L. ;
Mialet-Perez, Jeanne ;
Richardson, Gavin D. ;
Passos, Joao F. .
EMBO JOURNAL, 2019, 38 (05)
[4]   Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging [J].
Baar, Marjolein P. ;
Brandt, Renata M. C. ;
Putavet, Diana A. ;
Klein, Julian D. D. ;
Derks, Kasper W. J. ;
Bourgeois, Benjamin R. M. ;
Stryeck, Sarah ;
Rijksen, Yvonne ;
van Willigenburg, Hester ;
Feijtel, Danny A. ;
van der Pluijm, Ingrid ;
Essers, Jeroen ;
van Cappellen, Wiggert A. ;
van IJcken, Wilfred F. ;
Houtsmuller, Adriaan B. ;
Pothof, Joris ;
de Bruin, Ron W. F. ;
Madl, Tobias ;
Hoeijmakers, Jan H. J. ;
Campisi, Judith ;
de Keizer, Peter L. J. .
CELL, 2017, 169 (01) :132-+
[5]  
Baker DJ, 2017, ONCOTARGET, V8, P27661, DOI 10.18632/oncotarget.15742
[6]   Naturally occurring p16Ink4a-positive cells shorten healthy lifespan [J].
Baker, Darren J. ;
Childs, Bennett G. ;
Durik, Matej ;
Wijers, Melinde E. ;
Sieben, Cynthia J. ;
Zhong, Jian ;
Saltness, Rachel A. ;
Jeganathan, Karthik B. ;
Verzosa, Grace Casaclang ;
Pezeshki, Abdulmohammad ;
Khazaie, Khashayarsha ;
Miller, Jordan D. ;
van Deursen, Jan M. .
NATURE, 2016, 530 (7589) :184-+
[7]   Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders [J].
Baker, Darren J. ;
Wijshake, Tobias ;
Tchkonia, Tamar ;
LeBrasseur, Nathan K. ;
Childs, Bennett G. ;
van de Sluis, Bart ;
Kirkland, James L. ;
van Deursen, Jan M. .
NATURE, 2011, 479 (7372) :232-U112
[8]   A proteomic atlas of senescence-associated secretomes for aging biomarker development [J].
Basisty, Nathan ;
Kale, Abhijit ;
Jeon, Ok Hee ;
Kuehnemann, Chisaka ;
Payne, Therese ;
Rao, Chirag ;
Holtz, Anja ;
Shah, Samah ;
Sharma, Vagisha ;
Ferrucci, Luigi ;
Campisi, Judith ;
Schilling, Birgit .
PLOS BIOLOGY, 2020, 18 (01)
[9]   Senescence and the SASP: many therapeutic avenues [J].
Birch, Jodie ;
Gil, Jesus .
GENES & DEVELOPMENT, 2020, 34 (23-24) :1565-1576
[10]   A Senescence-Centric View of Aging Implications for Longevity and Disease [J].
Borghesan, M. ;
Hoogaars, W. M. H. ;
Varela-Eirin, M. ;
Talma, N. ;
Demaria, M. .
TRENDS IN CELL BIOLOGY, 2020, 30 (10) :777-791