Rapamycin for longevity: opinion article

被引:138
作者
Blagosklonny, Mikhail V. [1 ]
机构
[1] Roswell Park Canc Inst, Cell Stress Biol, Buffalo, NY 14263 USA
来源
AGING-US | 2019年 / 11卷 / 19期
关键词
rapamycin; rapalogs; metformin; aging; anti-aging; fasting; lifespan; health span; EXTENDS LIFE-SPAN; DIABETIC KIDNEY-DISEASE; LONG-TERM TREATMENT; MAMMALIAN TARGET; DIETARY RESTRICTION; INSULIN-RESISTANCE; TRANSPLANT RECIPIENTS; CELLULAR SENESCENCE; CALORIC RESTRICTION; MTOR INHIBITION;
D O I
10.18632/aging.102355
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
From the dawn of civilization, humanity has dreamed of immortality. So why didn't the discovery of the anti-aging properties of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as anti-aging drugs today. Furthermore, the alternative to the reversible (and avoidable) side effects of rapamycin/everolimus are the irreversible (and inevitable) effects of aging: cancer, stroke, infarction, blindness and premature death. I will also discuss why it is more dangerous not to use anti-aging drugs than to use them and how rapamycin-based drug combinations have already been implemented for potential life extension in humans. If you read this article from the very beginning to its end, you may realize that the time is now.
引用
收藏
页码:8048 / 8067
页数:20
相关论文
共 202 条
[91]   Rapamycin in aging and disease: maximizing efficacy while minimizing side effects [J].
Johnson, Simon C. ;
Kaeberlein, Matt .
ONCOTARGET, 2016, 7 (29) :44876-44878
[92]   Dose-dependent effects of mTOR inhibition on weight and mitochondrial disease in mice [J].
Johnson, Simon C. ;
Yanos, MelanaE. ;
Britto, Alessandro ;
Castanza, Anthony ;
Gagnidze, Arni ;
Gonzalez, Brenda ;
Gupta, Kanav ;
Hui, Jessica ;
Jarvie, Conner ;
Johnson, Brittany M. ;
Letexier, Nicolas ;
McCanta, Lanny ;
Sangesland, Maya ;
Tamis, Oliver ;
Uhde, Lauren ;
Van Den Ende, Alex ;
Rabinovitch, Peter S. ;
Suh, Yousin ;
Kaeberlein, Matt .
FRONTIERS IN GENETICS, 2015, 6
[93]   mTOR Inhibition Alleviates Mitochondrial Disease in a Mouse Model of Leigh Syndrome [J].
Johnson, Simon C. ;
Yanos, Melana E. ;
Kayser, Ernst-Bernhard ;
Quintana, Albert ;
Sangesland, Maya ;
Castanza, Anthony ;
Uhde, Lauren ;
Hui, Jessica ;
Wall, Valerie Z. ;
Gagnidze, Arni ;
Oh, Kelly ;
Wasko, Brian M. ;
Ramos, Fresnida J. ;
Palmiter, Richard D. ;
Rabinovitch, Peter S. ;
Morgan, Philip G. ;
Sedensky, Margaret M. ;
Kaeberlein, Matt .
SCIENCE, 2013, 342 (6165) :1524-1528
[94]   Sirolimus is associated with new-onset diabetes in kidney transplant recipients [J].
Johnston, Olwyn ;
Rose, Caren L. ;
Webster, Angela C. ;
Gill, John S. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2008, 19 (07) :1411-1418
[95]   Partial Inhibition of mTORC1 in Aged Rats Counteracts the Decline in Muscle Mass and Reverses Molecular Signaling Associated with Sarcopenia [J].
Joseph, Giselle A. ;
Wang, Sharon X. ;
Jacobs, Cody E. ;
Zhou, Weihua ;
Kimble, Garrett C. ;
Tse, Herman W. ;
Eash, John K. ;
Shavlakadze, Tea ;
Glass, David J. .
MOLECULAR AND CELLULAR BIOLOGY, 2019, 39 (19)
[96]   Clinically-Relevant Rapamycin Treatment Regimens Enhance CD8+ Effector Memory T Cell Function In The Skin and Allow their Infiltration into Cutaneous Squamous Cell Carcinoma [J].
Jung, Ji-Won ;
Veitch, Margaret ;
Bridge, Jennifer A. ;
Overgaard, Nana H. ;
Cruz, Jazmina L. ;
Linedale, Richard ;
Franklin, Michael E. ;
Saunders, Nicholas A. ;
Simpson, Fiona ;
Frazer, Ian H. ;
Steptoe, Raymond J. ;
Wells, James W. .
ONCOIMMUNOLOGY, 2018, 7 (09)
[97]   Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients [J].
Kaeberlein, M ;
Powers, RW ;
Steffen, KK ;
Westman, EA ;
Hu, D ;
Dang, N ;
Kerr, EO ;
Kirkland, KT ;
Fields, S ;
Kennedy, BK .
SCIENCE, 2005, 310 (5751) :1193-1196
[98]   Rapamycin and Ageing: When, for How Long, and How Much? [J].
Kaeberlein, Matt .
JOURNAL OF GENETICS AND GENOMICS, 2014, 41 (09) :459-463
[99]   Switch to an everolimus-facilitated cyclosporine A sparing immunosuppression improves glycemic control in selected kidney transplant recipients [J].
Kaelble, Florian ;
Seckinger, Joerg ;
Schaier, Matthias ;
Morath, Christian ;
Schwenger, Vedat ;
Zeier, Martin ;
Sommerer, Claudia .
CLINICAL TRANSPLANTATION, 2017, 31 (08)
[100]   Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway [J].
Kapahi, P ;
Zid, BM ;
Harper, T ;
Koslover, D ;
Sapin, V ;
Benzer, S .
CURRENT BIOLOGY, 2004, 14 (10) :885-890