Rapamycin in aging and disease: maximizing efficacy while minimizing side effects

被引：40

作者：

Johnson, Simon C. ^{[1
]}

Kaeberlein, Matt ^{[2
]}

机构：

[1] Albert Einstein Coll Med, Dept Genet, New York, NY USA

[2] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

来源：

ONCOTARGET | 2016年 / 7卷 / 29期

关键词：

mTOR; target of rapamycin; healthspan; mitochondria; mitochondria disease; MITOCHONDRIAL DISEASE; MTOR INHIBITION; LIFE-SPAN;

D O I：

10.18632/oncotarget.10381

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Experimental geroscience has identified rapamycin as a top candidate for promoting healthy aging and longevity in mammals. As multiple independent studies have successfully reproduced the lifespan and healthspan promoting effects of rapamycin, the focus has shifted to possible translational use. While a promising compound, clinical use of rapamycin is limited by concerns of side effects associated with the drug. Studies aimed at defining optimal dosage regimen, delivery route, and formulation will allow for benefits to be maximized while reducing side effects.

引用

页码：44876 / 44878

页数：3

共 10 条

[1] Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice [J].

Anisimov, Vladimir N. ;

Zabezhinski, Mark A. ;

Popovich, Irina G. ;

Piskunova, Tatiana S. ;

Semenchenko, Anna V. ;

Tyndyk, Margarita L. ;

Yurova, Maria N. ;

Rosenfeld, Svetlana V. ;

Blagosklonny, Mikhail V. .

CELL CYCLE, 2011, 10 (24) :4230-4236

[2] Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice [J].

Apelo, Sebastian I. Arriola ;

Pumper, Cassidy P. ;

Baar, Emma L. ;

Cummings, Nicole E. ;

Lamming, Dudley W. .

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2016, 71 (07) :876-881

[3] Rejuvenating immunity: "anti-aging drug today" eight years later [J].

Blagosklonny, Mikhail V. .

ONCOTARGET, 2015, 6 (23) :19405-19412

[4] 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

[5] 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

[6] mTOR is a key modulator of ageing and age-related disease [J].

Johnson, Simon C. ;

Rabinovitch, Peter S. ;

Kaeberlein, Matt .

NATURE, 2013, 493 (7432) :338-345

[7] The Biology of Aging: Citizen Scientists and Their Pets as a Bridge Between Research on Model Organisms and Human Subjects [J].

Kaeberlein, M. .

VETERINARY PATHOLOGY, 2016, 53 (02) :291-298

[8] mTOR Inhibition: From Aging to Autism and Beyond [J].

Kaeberlein, Matt .

SCIENTIFICA, 2013, 2013

[9] Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction [J].

Miller, Richard A. ;

Harrison, David E. ;

Astle, Clinton M. ;

Fernandez, Elizabeth ;

Flurkey, Kevin ;

Han, Melissa ;

Javors, Martin A. ;

Li, Xinna ;

Nadon, Nancy L. ;

Nelson, James F. ;

Pletcher, Scott ;

Salmon, Adam B. ;

Sharp, Zelton Dave ;

Van Roekel, Sabrina ;

Winkleman, Lynn ;

Strong, Randy .

AGING CELL, 2014, 13 (03) :468-477

[10] Rapamycin slows aging in mice [J].

Wilkinson, John E. ;

Burmeister, Lisa ;

Brooks, Susan V. ;

Chan, Chi-Chao ;

Friedline, Sabrina ;

Harrison, David E. ;

Hejtmancik, James F. ;

Nadon, Nancy ;

Strong, Randy ;

Wood, Lauren K. ;

Woodward, Maria A. ;

Miller, Richard A. .

AGING CELL, 2012, 11 (04) :675-682

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