Senolytics : A Potential Fountain of Youth.
DOI:
https://doi.org/10.55175/cdk.v46i2.511Keywords:
Senescent cells, senolyticsAbstract
Senolytics are groups of natural compounds, small molecules drugs and methods that eliminate senescent cells in the body of an organism. This review illustrate the pathogenesis or factors that lead to cellular senescence. As cellular senescence is the main culprit for age-associated diseases, the development of various classes of senolytics is of paramount importance in maintaining or even extending our health-span. Different classes of senolytics with some perspective of its potential for clinical applications will also be discussed.
Senolyitcs merupakan kelompok senyawa alami, obat dan metode yang melenyapkan sel-sel tua dari tubuh. Tinjauan ini membahas patogenesis dan faktor-faktor yang menyebabkan proses penuaan sel. Mengingat penuaan sel merupakan penyebab utama penyakit-penyakit akibat penuaan, pengembangan berbagai jenis senolytics sangat penting dalam upaya mempertahankan dan memperpanjang harapan hidup. Akan dibicarakan pula beberapa kelas senolytics beserta potensi klinisnya
Downloads
References
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell 2013;153:1194-217
van Deursen JM. The role of senescent cells in aging. Nature 2014; 509(7501):439-46
Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, et al. The Achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell 2015;14: 644-58
Kirkland JL, Tchkonia T. Clinical strategies and animal models for developing senolytic agents. Exp Gerontol. 2015;68:19-25. http://dx.doi.org/10.1016/j.exger.2014.10.012
Aan GJ, Hairi HA, Makpol S, Rahman MA, Karsani SA. Differences in protein changes between stress-induced premature senescence and replicative senescence states. Electrophoresis 2013;34:2201-17
Schnabl B, Purbeck CA, Choi YH, Hagedorn CH, Brenner D. Replicative senescence of activated hepatic stellate cells is accompanied by a pronounce inflammatory but less fibrogenic phenotype. Hepatology 2003; 37: 653-64
Bhatia-Dey N, Kanherkar RR, Stair SE, Makarev EO, Csoka AB. Cellular senescence as the causal nexus of aging. Front Genet. 2016;7:13.
Victorelli S, Passos JF. Telomeres and cell senescence – Size matters not. Ebiomedicine 2017;21:14-20
Bassaneze V, Miyakawa AA, Krieger JE. A quantitative chemiluminescent method for studying replicative and stress-induced premature senescence in cell culture. Anal Biochem 2007;372:198-203
Narita M. Cellular senescence and chromatin organization. Br J Cancer 2007; 96:686-91.
Brugat T, Nguyen-Khac F, Grelier A, Merle-BÏral H, Delic J. Telomere dysfunction foci arise with the onset of telomeric deletion and complex chromosomal aberration in resistant chronic lymphocytic leukemic cells. Blood 2007;116: 239-49
Kirkland JL, Tchkonia T, Zhu Y, Niedernhofer LJ, Robbins PD. The clinical potential of senolytic drugs. J Am Geriatr Soc. 2017;65(10):2297-301
Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, et al. New agents that target senescent cells: The flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Aging (Albany NY). 2017;9(3):955-63.
Wang Y, Chang J, Liu X, Zhang X, Zhang S, Zhang X, et al. Discovery of piperlongumine as a potential novel lead for the development of senolytic agents. Aging 2016; 8(11): 2915-26
Malavolta M, Pierpaoli E, Giacconi R, Costarelli L, Piacenza F, Basso A, et al. Pleiotropic effects of tocotrienols and quercetin on cellular senescence: Introducing the perspective of senolytic effects of phytochemicals. Curr Drug Target 2016;17(4):447-59
Rudder B. The effects of vitamin E isomer gamma tocopherol and gamma tocotrienol on thr NFkb pathway in PC-3 cell line [Thesis]. East Tennessee State: University Undergraduate Honor thesis; 2011
Lecumberri E, Dupertuis YM, Miralbell R, Pichard C. Green tea polyphenol epigallocatechin-3-gallate as adjuvant in cancer therapy. Clin Nutr. 2013; 32(6): 894-903
Spinozzi F, Pagliacci MC, Migliorati G, Moraca R, Grignani F, Riccardi C, et al. The natural tyrosine kinase inhibitor genistein produces cell cycle arrest and apoptosis in Jurkat T leukemic cells. Leukemia Res. 2004; 18 (6): 431-9
Perrott KM, Wiley CD, Desprez PY, Campisi J. Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells. Geroscience 2017;39: 161-73
Yi Zhu, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, et al. New agents that target senescence cells: the flavone, fisetin, and the BCL-XL inhibitors A1331852 and A1155463. Aging (Albany NY). 2017;9(3):955-63.
Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, et al. Identification of a novel senolytic agent, navitoclax, targeting the BCL-2 family of antiapoptotic factors. Aging Cell 2016;15: 428-35
Fuhrmann-Strissnigg H, Ling YY, Zhao J, McGowan SJ, Zhu Y, Brooks RW, et al. Identification of HSP90 inhibitors as a novel class of senolytics. Nature Comm. 2017;8:422
Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 2017;169(1):132-47
Chang J, Li Y, Huang Y, Lam KS, Hoo RL, Wong WT, et al. Adiponectin prevents diabetic premature senescence of endothelial progenitor cells and promotes endothelial repair by suppressing the p38 MAPKinase/p16-ink4a signaling pathway. Diabetes 2010;59(11):2949-59.
Yang G, Zhao K, Ju Y, Mani S, Cao Q, Puukila S, et al. Hydrogen sulfide protect against cellular senescence via S-Sulfhydration of Keap1 and activation of Nrf2. Antioxidants Redox Signaling 2013;18(15):1906-19
Bell J, McFadden G. Viruses for tumor therapy. Cell Host Microbe 2014;15(3):260-5.
Schafer MJ, White TA, Evans G, Tonne JM, Verzosa GC, Stout MB, et al. Exercise prevents diet-induced cellular senescence in adipose tissue. Diabetes 2016;65:1606-15
Jeon OH, Kim C, Laberge RM, Demaria M, Rathod S, Vasserot AP, et al. Local clearance of senescence cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nature Med. 2017;23:775-81
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 https://creativecommons.org/licenses/by-nc/4.0/
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
