Senolytic

A senolytic (from the words senescence and -lytic, "destroying") is among a class of small molecules under basic research to determine if they can selectively induce death of senescent cells and improve health in humans.[1] A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases.[2][3] A related concept is "senostatic", which means to suppress senescence.

Research

Possible senolytic agents are under preliminary research, including some which are in early-stage human trials.[4] The majority of candidate senolytic compounds are repurposed anti-cancer molecules, such as the chemotherapeutic drug dasatinib and the experimental small molecule navitoclax.[5][6]

Senolytic candidates

FOXO4-related peptides. FOXO4 binding to p53 protein retains it in the nucleus, which prevents it from interacting with mitochondria in the cytosol where it would activate caspases, leading to apoptosis (programmed cell death).[7] Instead, retention of p53 in the nucleus by FOXO4 promotes cellular senescence.[7] A peptide that binds with FOXO4 disrupts the p53-FOXO4 interaction, releasing p53 into the cytosol and triggering cell death.[7]
Inhibitors of different members of the bcl-2 family of anti-apoptotic proteins.[8] Studies of cell cultures of senescent human umbilical vein endothelial cells have shown that both fisetin and quercetin induce apoptosis by inhibition of the anti-apoptotic protein Bcl-xL (a bcl-2 family member).[9]
Src tyrosine kinase inhibitors.[10]
Inhibitors of USP7 (Ubiquitin-specific processing protease 7)[11]
Combination of dasatinib and quercetin[8][12][13]
Fisetin[14]
Navitoclax[15]
Piperlongumine[16]
Azithromycin and Roxithromycin[17]
SSK1 (senescence-specific killing compound 1): A gemcitabine (a cytotoxic chemotherapeutic) prodrug that is activated by lysosomal β-galactosidase (a common senescence marker)[18]
Crispr/Cas9 BIRC5 Gene Knockout: Crispr/Cas9 is used to trigger apoptosis in relation to a specified gene sequence such as a cancer gene sequence or damage marker sequences.[19]
Target the enzyme kidney-type glutaminase 1 (GLS1). Senescent cells have a low pH due to their high lysosomal content and leaking lysosomal membranes. This low pH forms the basis of senescence-associated beta-galactosidase (SA-β-gal) staining of senescent cells. To help neutralize their low pH, senescent cells produce high levels of GLS1; inhibiting the activity of this enzyme exposes senescent cells to unsurvivably severe internal acidity, leading to cell death.[20]
Glycoprotein nonmetastatic melanoma protein B (GPNMB): a protein that enrich senescent cells studied as molecular target for a senolytic vaccine.[21][22]
Cardiac glycosides[23][24][25].

References

Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M (8 December 2015). "Cellular senescence in aging and age-related disease: from mechanisms to therapy". Nature Medicine. 21 (12): 1424–1435. doi:10.1038/nm.4000. PMC 4748967. PMID 26646499.
Kirkland, James L.; Tchkonia, Tamara (August 2015). "Clinical strategies and animal models for developing senolytic agents". Experimental Gerontology. 68: 19–25. doi:10.1016/j.exger.2014.10.012. PMC 4412760. PMID 25446976.
van Deursen, Jan M. (16 May 2019). "Senolytic therapies for healthy longevity". Science. 364 (6441): 636–637. Bibcode:2019Sci...364..636V. doi:10.1126/science.aaw1299. PMC 6816502. PMID 31097655.
Baumann, Kim (27 July 2018). "Rejuvenating senolytics". Nature Reviews Molecular Cell Biology. 19 (9): 543. doi:10.1038/s41580-018-0047-5. PMID 30054558. S2CID 51726136.
Blagosklonny, Mikhail V (28 October 2014). "Selective anti-cancer agents as anti-aging drugs". Cancer Biology & Therapy. 14 (12): 1092–1097. doi:10.4161/cbt.27350. PMC 3912031. PMID 24345884.
Slack, Cathy; Alic, Nazif; Partridge, Linda (6 January 2016). "Could cancer drugs provide ammunition against aging?". Cell Cycle. 15 (2): 153–155. doi:10.1080/15384101.2015.1118905. PMC 4825846. PMID 26587873.
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. (March 2017). "Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging". Cell. 169 (1): 132–147.e16. doi:10.1016/j.cell.2017.02.031. PMC 5556182. PMID 28340339.
Hernandez-Segura, Alejandra; Nehme, Jamil; Demaria, Marco (June 2018). "Hallmarks of Cellular Senescence" (PDF). Trends in Cell Biology. 28 (6): 436–453. doi:10.1016/j.tcb.2018.02.001. PMID 29477613.
Kirkland JL, Tchkonia T (2020). "Senolytic drugs: from discovery to translation". Journal of Internal Medicine. 288 (5): 518–536. doi:10.1111/joim.13141. PMC 7405395. PMID 32686219.
Rivera-Torres J, José ES (2019). "Src Tyrosine Kinase Inhibitors: New Perspectives on Their Immune, Antiviral, and Senotherapeutic Potential". Frontiers in Pharmacology. 10: 1011. doi:10.3389/fphar.2019.01011. PMC 6759511. PMID 31619990.
He, Yonghan; Li, Wen; Lv, Dongwen; Zhang, Xin; Zhang, Xuan; Ortiz, Yuma T.; Budamagunta, Vivekananda; Campisi, Judith; Zheng, Guangrong; Zhou, Daohong (16 February 2020). "Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity". Aging Cell. 19 (3): e13117. doi:10.1111/acel.13117. PMC 7059172. PMID 32064756.
Hickson, LaTonya J.; Langhi Prata, Larissa G.P.; Bobart, Shane A.; Evans, Tamara K.; Giorgadze, Nino; Hashmi, Shahrukh K.; Herrmann, Sandra M.; Jensen, Michael D.; Jia, Qingyi; Jordan, Kyra L.; Kellogg, Todd A.; Khosla, Sundeep; Koerber, Daniel M.; Lagnado, Anthony B.; Lawson, Donna K.; LeBrasseur, Nathan K.; Lerman, Lilach O.; McDonald, Kathleen M.; McKenzie, Travis J.; Passos, João F.; Pignolo, Robert J.; Pirtskhalava, Tamar; Saadiq, Ishran M.; Schaefer, Kalli K.; Textor, Stephen C.; Victorelli, Stella G.; Volkman, Tammie L.; Xue, Ailing; Wentworth, Mark A.; Wissler Gerdes, Erin O.; Zhu, Yi; Tchkonia, Tamara; Kirkland, James L. (September 2019). "Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease". EBioMedicine. 47: 446–456. doi:10.1016/j.ebiom.2019.08.069. PMC 6796530. PMID 31542391.
Palmer AK, Gustafson B, Kirkland JL, Smith U (2019). "Cellular senescence: at the nexus between ageing and diabetes". Diabetologia. 62 (10): 1835–1841. doi:10.1007/s00125-019-4934-x. PMC 6731336. PMID 31451866.
Yousefzadeh, Matthew J.; Zhu, Yi; McGowan, Sara J.; Angelini, Luise; Fuhrmann-Stroissnigg, Heike; Xu, Ming; Ling, Yuan Yuan; Melos, Kendra I.; Pirtskhalava, Tamar; Inman, Christina L.; McGuckian, Collin; Wade, Erin A.; Kato, Jonathon I.; Grassi, Diego; Wentworth, Mark; Burd, Christin E.; Arriaga, Edgar A.; Ladiges, Warren L.; Tchkonia, Tamara; Kirkland, James L.; Robbins, Paul D.; Niedernhofer, Laura J. (October 2018). "Fisetin is a senotherapeutic that extends health and lifespan". EBioMedicine. 36: 18–28. doi:10.1016/j.ebiom.2018.09.015. PMC 6197652. PMID 30279143.
Shoemaker, Alex R.; Mitten, Michael J.; Adickes, Jessica; Ackler, Scott; Refici, Marion; Ferguson, Debra; Oleksijew, Anatol; O'Connor, Jacqueline M.; Wang, Baole; Frost, David J.; Bauch, Joy; Marsh, Kennan; Tahir, Steven K.; Yang, Xiufen; Tse, Christin; Fesik, Stephen W.; Rosenberg, Saul H.; Elmore, Steven W. (1 June 2008). "Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models". Clinical Cancer Research. 14 (11): 3268–3277. doi:10.1158/1078-0432.CCR-07-4622. PMID 18519752.
Wang, Yingying; Chang, Jianhui; Liu, Xingui; Zhang, Xuan; Zhang, Suping; Zhang, Xin; Zhou, Daohong; Zheng, Guangrong (19 November 2016). "Discovery of piperlongumine as a potential novel lead for the development of senolytic agents". Aging. 8 (11): 2915–2926. doi:10.18632/aging.101100. PMC 5191878. PMID 27913811.
Ozsvari, Bela; Nuttall, John R.; Sotgia, Federica; Lisanti, Michael P. (14 November 2018). "Azithromycin and Roxithromycin define a new family of "senolytic" drugs that target senescent human fibroblasts". Aging. 10 (11): 3294–3307. doi:10.18632/aging.101633. PMC 6286845. PMID 30428454.
Cai, Yusheng; Zhou, Huanhuan; Zhu, Yinhua; Sun, Qi; Ji, Yin; Xue, Anqi; Wang, Yuting; Chen, Wenhan; Yu, Xiaojie; Wang, Longteng; Chen, Han; Li, Cheng; Luo, Tuoping; Deng, Hongkui (27 April 2020). "Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice". Cell Research. 30 (7): 574–589. doi:10.1038/s41422-020-0314-9. PMC 7184167. PMID 32341413.
Narimani, Manizheh; Sharifi, Mohammadreza; Jalili, Ali (2019-11-27). "Knockout Of BIRC5 Gene By CRISPR/Cas9 Induces Apoptosis And Inhibits Cell Proliferation In Leukemic Cell Lines, HL60 And KG1". Blood and Lymphatic Cancer: Targets and Therapy. 9: 53–61. doi:10.2147/BLCTT.S230383. ISSN 1179-9889. PMC 6885567. PMID 31819702.
Johmura, Yoshikazu; Yamanaka, Takehiro; Omori, Satotaka; Wang, Teh-Wei; Sugiura, Yuki; Matsumoto, Masaki; Suzuki, Narumi; Kumamoto, Soichiro; Yamaguchi, Kiyoshi; Hatakeyama, Seira; Takami, Tomoyo (2021-01-15). "Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders". Science. 371 (6526): 265–270. Bibcode:2021Sci...371..265J. doi:10.1126/science.abb5916. ISSN 0036-8075. PMID 33446552. S2CID 231606800.
"Japanese scientists develop vaccine to eliminate cells behind aging". Japan Times. 12 December 2021. Retrieved 12 December 2021.
"Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice". Nature Aging. 10 December 2021. Retrieved 12 December 2021.
L’Hôte, Valentin; Courbeyrette, Régis; Pinna, Guillaume; Cintrat, Jean-Christophe; Pavec, Gwenaëlle Le; Delaunay-Moisan, Agnès; Mann, Carl; Thuret, Jean-Yves (2021). "Ouabain and chloroquine trigger senolysis of BRAF-V600E-induced senescent cells by targeting autophagy". Aging Cell. 20 (9): e13447. doi:10.1111/acel.13447. ISSN 1474-9726. PMC 8564827. PMID 34355491.
Triana-Martínez, Francisco; Picallos-Rabina, Pilar; Da Silva-Álvarez, Sabela; Pietrocola, Federico; Llanos, Susana; Rodilla, Verónica; Soprano, Enrica; Pedrosa, Pablo; Ferreirós, Alba; Barradas, Marta; Hernández-González, Fernanda (2019-12). "Identification and characterization of Cardiac Glycosides as senolytic compounds". Nature Communications. 10 (1): 4731. doi:10.1038/s41467-019-12888-x. ISSN 2041-1723. PMC 6803708. PMID 31636264. Check date values in: |date= (help)
Guerrero, Ana; Herranz, Nicolás; Sun, Bin; Wagner, Verena; Gallage, Suchira; Guiho, Romain; Wolter, Katharina; Pombo, Joaquim; Irvine, Elaine E.; Innes, Andrew J.; Birch, Jodie (2019-11). "Cardiac glycosides are broad-spectrum senolytics". Nature Metabolism. 1 (11): 1074–1088. doi:10.1038/s42255-019-0122-z. ISSN 2522-5812. PMC 6887543. PMID 31799499. Check date values in: |date= (help)

External links

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[pmid26646499-1] Childs, Bennett G; Durik, Matej; Baker, Darren J; van Deursen, Jan M (8 December 2015). "Cellular senescence in aging and age-related disease: from mechanisms to therapy". Nature Medicine. 21 (12): 1424–1435. doi:10.1038/nm.4000. PMC 4748967. PMID 26646499.

[pmid25446976-2] Kirkland, James L.; Tchkonia, Tamara (August 2015). "Clinical strategies and animal models for developing senolytic agents". Experimental Gerontology. 68: 19–25. doi:10.1016/j.exger.2014.10.012. PMC 4412760. PMID 25446976.

[3] van Deursen, Jan M. (16 May 2019). "Senolytic therapies for healthy longevity". Science. 364 (6441): 636–637. Bibcode:2019Sci...364..636V. doi:10.1126/science.aaw1299. PMC 6816502. PMID 31097655.

[4] Baumann, Kim (27 July 2018). "Rejuvenating senolytics". Nature Reviews Molecular Cell Biology. 19 (9): 543. doi:10.1038/s41580-018-0047-5. PMID 30054558. S2CID 51726136.

[pmid24345884-5] Blagosklonny, Mikhail V (28 October 2014). "Selective anti-cancer agents as anti-aging drugs". Cancer Biology & Therapy. 14 (12): 1092–1097. doi:10.4161/cbt.27350. PMC 3912031. PMID 24345884.

[pmid26587873-6] Slack, Cathy; Alic, Nazif; Partridge, Linda (6 January 2016). "Could cancer drugs provide ammunition against aging?". Cell Cycle. 15 (2): 153–155. doi:10.1080/15384101.2015.1118905. PMC 4825846. PMID 26587873.

[pmid28340339-7] 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. (March 2017). "Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging". Cell. 169 (1): 132–147.e16. doi:10.1016/j.cell.2017.02.031. PMC 5556182. PMID 28340339.

[pmid29477613-8] Hernandez-Segura, Alejandra; Nehme, Jamil; Demaria, Marco (June 2018). "Hallmarks of Cellular Senescence" (PDF). Trends in Cell Biology. 28 (6): 436–453. doi:10.1016/j.tcb.2018.02.001. PMID 29477613.

[pmid32686219-9] Kirkland JL, Tchkonia T (2020). "Senolytic drugs: from discovery to translation". Journal of Internal Medicine. 288 (5): 518–536. doi:10.1111/joim.13141. PMC 7405395. PMID 32686219.

[pmid31619990-10] Rivera-Torres J, José ES (2019). "Src Tyrosine Kinase Inhibitors: New Perspectives on Their Immune, Antiviral, and Senotherapeutic Potential". Frontiers in Pharmacology. 10: 1011. doi:10.3389/fphar.2019.01011. PMC 6759511. PMID 31619990.

[pmid32064756-11] He, Yonghan; Li, Wen; Lv, Dongwen; Zhang, Xin; Zhang, Xuan; Ortiz, Yuma T.; Budamagunta, Vivekananda; Campisi, Judith; Zheng, Guangrong; Zhou, Daohong (16 February 2020). "Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity". Aging Cell. 19 (3): e13117. doi:10.1111/acel.13117. PMC 7059172. PMID 32064756.

[pmid31542391-12] Hickson, LaTonya J.; Langhi Prata, Larissa G.P.; Bobart, Shane A.; Evans, Tamara K.; Giorgadze, Nino; Hashmi, Shahrukh K.; Herrmann, Sandra M.; Jensen, Michael D.; Jia, Qingyi; Jordan, Kyra L.; Kellogg, Todd A.; Khosla, Sundeep; Koerber, Daniel M.; Lagnado, Anthony B.; Lawson, Donna K.; LeBrasseur, Nathan K.; Lerman, Lilach O.; McDonald, Kathleen M.; McKenzie, Travis J.; Passos, João F.; Pignolo, Robert J.; Pirtskhalava, Tamar; Saadiq, Ishran M.; Schaefer, Kalli K.; Textor, Stephen C.; Victorelli, Stella G.; Volkman, Tammie L.; Xue, Ailing; Wentworth, Mark A.; Wissler Gerdes, Erin O.; Zhu, Yi; Tchkonia, Tamara; Kirkland, James L. (September 2019). "Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease". EBioMedicine. 47: 446–456. doi:10.1016/j.ebiom.2019.08.069. PMC 6796530. PMID 31542391.

[pmid31451866-13] Palmer AK, Gustafson B, Kirkland JL, Smith U (2019). "Cellular senescence: at the nexus between ageing and diabetes". Diabetologia. 62 (10): 1835–1841. doi:10.1007/s00125-019-4934-x. PMC 6731336. PMID 31451866.

[pmid30279143-14] Yousefzadeh, Matthew J.; Zhu, Yi; McGowan, Sara J.; Angelini, Luise; Fuhrmann-Stroissnigg, Heike; Xu, Ming; Ling, Yuan Yuan; Melos, Kendra I.; Pirtskhalava, Tamar; Inman, Christina L.; McGuckian, Collin; Wade, Erin A.; Kato, Jonathon I.; Grassi, Diego; Wentworth, Mark; Burd, Christin E.; Arriaga, Edgar A.; Ladiges, Warren L.; Tchkonia, Tamara; Kirkland, James L.; Robbins, Paul D.; Niedernhofer, Laura J. (October 2018). "Fisetin is a senotherapeutic that extends health and lifespan". EBioMedicine. 36: 18–28. doi:10.1016/j.ebiom.2018.09.015. PMC 6197652. PMID 30279143.

[pmid18519752-15] Shoemaker, Alex R.; Mitten, Michael J.; Adickes, Jessica; Ackler, Scott; Refici, Marion; Ferguson, Debra; Oleksijew, Anatol; O'Connor, Jacqueline M.; Wang, Baole; Frost, David J.; Bauch, Joy; Marsh, Kennan; Tahir, Steven K.; Yang, Xiufen; Tse, Christin; Fesik, Stephen W.; Rosenberg, Saul H.; Elmore, Steven W. (1 June 2008). "Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models". Clinical Cancer Research. 14 (11): 3268–3277. doi:10.1158/1078-0432.CCR-07-4622. PMID 18519752.

[16] Wang, Yingying; Chang, Jianhui; Liu, Xingui; Zhang, Xuan; Zhang, Suping; Zhang, Xin; Zhou, Daohong; Zheng, Guangrong (19 November 2016). "Discovery of piperlongumine as a potential novel lead for the development of senolytic agents". Aging. 8 (11): 2915–2926. doi:10.18632/aging.101100. PMC 5191878. PMID 27913811.

[17] Ozsvari, Bela; Nuttall, John R.; Sotgia, Federica; Lisanti, Michael P. (14 November 2018). "Azithromycin and Roxithromycin define a new family of "senolytic" drugs that target senescent human fibroblasts". Aging. 10 (11): 3294–3307. doi:10.18632/aging.101633. PMC 6286845. PMID 30428454.

[18] Cai, Yusheng; Zhou, Huanhuan; Zhu, Yinhua; Sun, Qi; Ji, Yin; Xue, Anqi; Wang, Yuting; Chen, Wenhan; Yu, Xiaojie; Wang, Longteng; Chen, Han; Li, Cheng; Luo, Tuoping; Deng, Hongkui (27 April 2020). "Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice". Cell Research. 30 (7): 574–589. doi:10.1038/s41422-020-0314-9. PMC 7184167. PMID 32341413.

[19] Narimani, Manizheh; Sharifi, Mohammadreza; Jalili, Ali (2019-11-27). "Knockout Of BIRC5 Gene By CRISPR/Cas9 Induces Apoptosis And Inhibits Cell Proliferation In Leukemic Cell Lines, HL60 And KG1". Blood and Lymphatic Cancer: Targets and Therapy. 9: 53–61. doi:10.2147/BLCTT.S230383. ISSN 1179-9889. PMC 6885567. PMID 31819702.

[Johmura2021-20] Johmura, Yoshikazu; Yamanaka, Takehiro; Omori, Satotaka; Wang, Teh-Wei; Sugiura, Yuki; Matsumoto, Masaki; Suzuki, Narumi; Kumamoto, Soichiro; Yamaguchi, Kiyoshi; Hatakeyama, Seira; Takami, Tomoyo (2021-01-15). "Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders". Science. 371 (6526): 265–270. Bibcode:2021Sci...371..265J. doi:10.1126/science.abb5916. ISSN 0036-8075. PMID 33446552. S2CID 231606800.

[21] "Japanese scientists develop vaccine to eliminate cells behind aging". Japan Times. 12 December 2021. Retrieved 12 December 2021.

[22] "Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice". Nature Aging. 10 December 2021. Retrieved 12 December 2021.

[23] L’Hôte, Valentin; Courbeyrette, Régis; Pinna, Guillaume; Cintrat, Jean-Christophe; Pavec, Gwenaëlle Le; Delaunay-Moisan, Agnès; Mann, Carl; Thuret, Jean-Yves (2021). "Ouabain and chloroquine trigger senolysis of BRAF-V600E-induced senescent cells by targeting autophagy". Aging Cell. 20 (9): e13447. doi:10.1111/acel.13447. ISSN 1474-9726. PMC 8564827. PMID 34355491.

[24] Triana-Martínez, Francisco; Picallos-Rabina, Pilar; Da Silva-Álvarez, Sabela; Pietrocola, Federico; Llanos, Susana; Rodilla, Verónica; Soprano, Enrica; Pedrosa, Pablo; Ferreirós, Alba; Barradas, Marta; Hernández-González, Fernanda (2019-12). "Identification and characterization of Cardiac Glycosides as senolytic compounds". Nature Communications. 10 (1): 4731. doi:10.1038/s41467-019-12888-x. ISSN 2041-1723. PMC 6803708. PMID 31636264. Check date values in: |date= (help)

[25] Guerrero, Ana; Herranz, Nicolás; Sun, Bin; Wagner, Verena; Gallage, Suchira; Guiho, Romain; Wolter, Katharina; Pombo, Joaquim; Irvine, Elaine E.; Innes, Andrew J.; Birch, Jodie (2019-11). "Cardiac glycosides are broad-spectrum senolytics". Nature Metabolism. 1 (11): 1074–1088. doi:10.1038/s42255-019-0122-z. ISSN 2522-5812. PMC 6887543. PMID 31799499. Check date values in: |date= (help)

Senolytic

Research

Senolytic candidates

See also

References

External links