Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to

被引:67
作者
Blagosklonny, Mikhail V. [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA
来源
AGING-US | 2012年 / 4卷 / 05期
关键词
aging; diabetes; retinopathy; nephropathy; diseases; anti-aging drugs; growth hormone; POSTTRANSPLANT DIABETES-MELLITUS; EXTENDS LIFE-SPAN; MAMMALIAN TARGET; GLUCOSE-TOLERANCE; KIDNEY-TRANSPLANTATION; BETA-CELLS; RECEPTOR SUBSTRATE-1; CALORIE RESTRICTION; SIGNALING PATHWAY; SKELETAL-MUSCLE;
D O I
10.18632/aging.100461
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Calorie restriction (CR), which deactivates the nutrient-sensing mTOR pathway, slows down aging and prevents age-related diseases such as type II diabetes. Compared with CR, rapamycin more efficiently inhibits mTOR. Noteworthy, severe CR and starvation cause a reversible condition known as "starvation diabetes." As was already discussed, chronic administration of rapamycin can cause a similar condition in some animal models. A recent paper published in Science reported that chronic treatment with rapamycin causes a diabetes-like condition in mice by indirectly inhibiting mTOR complex 2. Here I introduce the notion of benevolent diabetes and discuss whether starvation-like effects of chronic high dose treatment with rapamycin are an obstacle for its use as an anti-aging drug.
引用
收藏
页码:350 / 358
页数:9
相关论文
共 103 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]
Rapamycin Extends Maximal Lifespan in Cancer-Prone Mice [J].
Anisimov, Vladimir N. ;
Zabezhinski, Mark A. ;
Popovich, Irina G. ;
Piskunova, Tatiana S. ;
Semenchenko, Anna V. ;
Tyndyk, Margarita L. ;
Yurova, Maria N. ;
Antoch, Marina P. ;
Blagosklonny, Mikhail V. .
AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (05) :2092-2097
[3]
Posttransplant diabetes mellitus in kidney transplant recipients receiving calcineurin or mTOR inhibitor drugs [J].
Araki, M ;
Flechner, SM ;
Ismail, HR ;
Flechner, LM ;
Zhou, LM ;
Derweesh, IH ;
Goldfarb, D ;
Modlin, C ;
Novick, AC ;
Faiman, C .
TRANSPLANTATION, 2006, 81 (03) :335-341
[4]
Long-lived Klotho mice: new insights into the roles of IGF-1 and insulin-in aging [J].
Bartke, A .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2006, 17 (02) :33-35
[5]
Bartke A, 2012, HLTH AGING IS SMALLE
[6]
Pleiotropic effects of growth hormone signaling in aging [J].
Bartke, Andrzej .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2011, 22 (11) :437-442
[7]
Single-gene mutations and healthy ageing in mammals [J].
Bartke, Andrzej .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2011, 366 (1561) :28-34
[8]
Surgical removal of visceral fat reverses hepatic insulin resistance [J].
Barzilai, N ;
She, L ;
Liu, BQ ;
Vuguin, P ;
Cohen, P ;
Wang, JL ;
Rossetti, L .
DIABETES, 1999, 48 (01) :94-98
[9]
The Critical Role of Metabolic Pathways in Aging [J].
Barzilai, Nir ;
Huffman, Derek M. ;
Muzumdar, Radhika H. ;
Bartke, Andrzej .
DIABETES, 2012, 61 (06) :1315-1322
[10]
Rapamycin passes the torch: a new generation of mTOR inhibitors [J].
Benjamin, Don ;
Colombi, Marco ;
Moroni, Christoph ;
Hall, Michael N. .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (11) :868-880