反老藥(Senolytic)是一類受到基礎科學研究以確定其是否能選擇性地殺死衰老細胞並增進人體健康的小分子物質;[1]這類研究的目標是找出或開發能延緩、阻止、紓解甚至逆轉老化相關疾病的藥物。[2][3]與此類研究相關的一個概念是「凍齡」(senostatic),其意為抑制老化。
目前對返老藥的研究處於初步階段,其中一些已經進入人體試驗階段的早期。[4]目前多數潛在的返老藥,其原本的目的是用作抗癌藥物,像是用於化療的藥物达沙替尼以及實驗性的小分子藥物那維托克(Navitoclax,ABT-263)等是其中的例子。[5][6]
盡管目前只有少數的返老藥進入臨床測試的階段,但一項人體初步臨床試驗顯示,达沙替尼和槲皮素的混合物在患有糖尿病腎臟病變的人類患者中,確會降低部分組織當中衰老細胞的數量。[10]
- 自噬
- 老化防護(Geroprotector)
- 维奈托克(Venetoclax)
- 抗衰老治療(Senotherapy)
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. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. March 2017, 169 (1): 132–147.e16. PMC 5556182 . PMID 28340339. doi:10.1016/j.cell.2017.02.031.
He, Yonghan; Li, Wen; Lv, Dongwen; Zhang, Xin; Zhang, Xuan; Ortiz, Yuma T.; Budamagunta, Vivekananda; Campisi, Judith; Zheng, Guangrong; Zhou, Daohong. Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity. Aging Cell. 16 February 2020, 19 (3): e13117. PMC 7059172 . PMID 32064756. doi:10.1111/acel.13117.
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. Senolytics decrease senescent cells in humans: Preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. September 2019, 47: 446–456. PMC 6796530 . PMID 31542391. doi:10.1016/j.ebiom.2019.08.069.
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. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. October 2018, 36: 18–28. PMC 6197652 . PMID 30279143. doi:10.1016/j.ebiom.2018.09.015.
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. Activity of the Bcl-2 Family Inhibitor ABT-263 in a Panel of Small Cell Lung Cancer Xenograft Models. Clinical Cancer Research. 1 June 2008, 14 (11): 3268–3277. PMID 18519752. doi:10.1158/1078-0432.CCR-07-4622.
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. Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice. Cell Research. 27 April 2020: 1–16. PMC 7184167 . PMID 32341413. doi:10.1038/s41422-020-0314-9.