Rapamycin extends life- and health span because it slows aging

被引：64

作者：

Blagosklonny, Mikhail V. ^{[1
]}

机构：

[1] Roswell Pk Canc Inst, Dept Cell Stress Biol, BLSC, Buffalo, NY 14263 USA

来源：

AGING-US | 2013年 / 5卷 / 08期

关键词：

murine lifespan; mammalian target of rapamycin; rapalogs; diseases; age-relayed pathology; AGE-RELATED DISEASES; FATAL NEOPLASTIC DISEASES; HEMATOPOIETIC STEM-CELLS; NAKED MOLE-RAT; CELLULAR SENESCENCE; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; MTOR-INHIBITOR; SPONTANEOUS TUMORIGENESIS; P53-DEFICIENT MICE;

D O I：

10.18632/aging.100591

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Making headlines, a thought-provocative paper by Neff, Ehninger and coworkers claims that rapamycin extends life span but has limited effects on aging. How is that possibly possible? And what is aging if not an increase of the probability of death with age. I discuss that the JCI paper actually shows that rapamycin slows aging and also extends lifespan regardless of its direct anti-cancer activities. Aging is, in part, MTOR-driven: a purposeless continuation of developmental growth. Rapamycin affects the same processes in young and old animals: young animals' traits and phenotypes, which continuations become hyperfunctional, harmful and lethal later in life.

引用

页码：592 / 598

页数：7

共 141 条

[91] Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control [J].

Loewith, Robbie ;

Hall, Michael N. .

GENETICS, 2011, 189 (04) :1177-1201

[92] The Hallmarks of Aging [J].

Lopez-Otin, Carlos ;

Blasco, Maria A. ;

Partridge, Linda ;

Serrano, Manuel ;

Kroemer, Guido .

CELL, 2013, 153 (06) :1194-1217

[93] Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment [J].

Martelli, Alberto M. ;

Chiarini, Francesca ;

Evangelisti, Camilla ;

Cappellini, Alessandra ;

Buontempo, Francesca ;

Bressanin, Daniela ;

Fini, Milena ;

McCubrey, James A. .

ONCOTARGET, 2012, 3 (04) :371-394

[94] Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance [J].

McCubrey, James A. ;

Steelman, Linda S. ;

Chappell, William H. ;

Abrams, Stephen L. ;

Franklin, Richard A. ;

Montalto, Giuseppe ;

Cervello, Melchiorre ;

Libra, Massimo ;

Candido, Saverio ;

Malaponte, Grazia ;

Mazzarino, Maria C. ;

Fagone, Paolo ;

Nicoletti, Ferdinando ;

Baesecke, Joerg ;

Mijatovic, Sanja ;

Maksimovic-Ivanic, Danijela ;

Milella, Michele ;

Tafuri, Agostino ;

Chiarini, Francesca ;

Evangelisti, Camilla ;

Cocco, Lucio ;

Martelli, Alberto M. .

ONCOTARGET, 2012, 3 (10) :1068-1111

[95] cep-1/p53-dependent dysplastic pathology of the aging C. elegans gonad [J].

McGee, Mathew D. ;

Day, Nicholas ;

Graham, Jill ;

Melov, Simon .

AGING-US, 2012, 4 (04) :256-269

[96]

Mehta R, 2010, ADV EXP MED BIOL, V694, P14

[97] mTOR-regulated senescence and autophagy during reprogramming of somatic cells to pluripotency A roadmap from energy metabolism to stem cell renewal and aging [J].

Menendez, Javier A. ;

Vellon, Luciano ;

Oliveras-Ferraros, Cristina ;

Cufi, Silvia ;

Vazquez-Martin, Alejandro .

CELL CYCLE, 2011, 10 (21) :3658-3677

[98] Caveolin-1 and Accelerated Host Aging in the Breast Tumor Microenvironment Chemoprevention with Rapamycin, an mTOR Inhibitor and Anti-Aging Drug [J].

Mercier, Isabelle ;

Camacho, Jeanette ;

Titchen, Kanani ;

Gonzales, Donna M. ;

Quann, Kevin ;

Bryant, Kelly G. ;

Molchansky, Alexander ;

Milliman, Janet N. ;

Whitaker-Menezes, Diana ;

Sotgia, Federica ;

Jasmin, Jean-Francois ;

Schwarting, Roland ;

Pestell, Richard G. ;

Blagosklonny, Mikhail V. ;

Lisanti, Michael P. .

AMERICAN JOURNAL OF PATHOLOGY, 2012, 181 (01) :278-293

[99] Modeling age-related diseases in Drosophila:: Can this fly? [J].

Michno, K ;

van de Hoef, D ;

Wu, H ;

Boulianne, GL .

CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 71, 2005, 71 :199-223

[100] Pharmacological Inhibition of Phosphoinositide 3 and TOR Kinases Improves Survival of Drosophila melanogaster [J].

Moskalev, A. A. ;

Shaposhnikov, M. V. .

REJUVENATION RESEARCH, 2010, 13 (2-3) :246-247

← 5 6 7 8 9 10 11 12 13 14 →