Literature DB >> 27091134

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

Sebastian I Arriola Apelo1, Cassidy P Pumper1, Emma L Baar1, Nicole E Cummings2, Dudley W Lamming3.   

Abstract

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans.
© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Entities:  

Keywords:  Anti-aging; Life span; Mice; Rapamycin; mTOR

Mesh:

Substances:

Year:  2016        PMID: 27091134      PMCID: PMC4906329          DOI: 10.1093/gerona/glw064

Source DB:  PubMed          Journal:  J Gerontol A Biol Sci Med Sci        ISSN: 1079-5006            Impact factor:   6.053


  43 in total

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Authors:  Chenxi Wang; Qing Li; David T Redden; Richard Weindruch; David B Allison
Journal:  Mech Ageing Dev       Date:  2004-09       Impact factor: 5.432

2.  Rapamycin extends maximal lifespan in cancer-prone mice.

Authors:  Vladimir N Anisimov; Mark A Zabezhinski; Irina G Popovich; Tatiana S Piskunova; Anna V Semenchenko; Margarita L Tyndyk; Maria N Yurova; Marina P Antoch; Mikhail V Blagosklonny
Journal:  Am J Pathol       Date:  2010-04-02       Impact factor: 4.307

3.  Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue.

Authors:  Vanessa P Houde; Sophie Brûlé; William T Festuccia; Pierre-Gilles Blanchard; Kerstin Bellmann; Yves Deshaies; André Marette
Journal:  Diabetes       Date:  2010-03-18       Impact factor: 9.461

4.  Duration of rapamycin treatment has differential effects on metabolism in mice.

Authors:  Yimin Fang; Reyhan Westbrook; Cristal Hill; Ravneet K Boparai; Oge Arum; Adam Spong; Feiya Wang; Martin A Javors; Jie Chen; Liou Y Sun; Andrzej Bartke
Journal:  Cell Metab       Date:  2013-03-05       Impact factor: 27.287

5.  Rapamycin extends life and health in C57BL/6 mice.

Authors:  Yiqiang Zhang; Alex Bokov; John Gelfond; Vanessa Soto; Yuji Ikeno; Gene Hubbard; Vivian Diaz; Lauren Sloane; Keith Maslin; Stephen Treaster; Samantha Réndon; Holly van Remmen; Walter Ward; Martin Javors; Arlan Richardson; Steven N Austad; Kathleen Fischer
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2013-05-16       Impact factor: 6.053

6.  Rapamycin extends murine lifespan but has limited effects on aging.

Authors:  Frauke Neff; Diana Flores-Dominguez; Devon P Ryan; Marion Horsch; Susanne Schröder; Thure Adler; Luciana Caminha Afonso; Juan Antonio Aguilar-Pimentel; Lore Becker; Lillian Garrett; Wolfgang Hans; Moritz M Hettich; Richard Holtmeier; Sabine M Hölter; Kristin Moreth; Cornelia Prehn; Oliver Puk; Ildikó Rácz; Birgit Rathkolb; Jan Rozman; Beatrix Naton; Rainer Ordemann; Jerzy Adamski; Johannes Beckers; Raffi Bekeredjian; Dirk H Busch; Gerhard Ehninger; Jochen Graw; Heinz Höfler; Martin Klingenspor; Thomas Klopstock; Markus Ollert; Jörg Stypmann; Eckhard Wolf; Wolfgang Wurst; Andreas Zimmer; Helmut Fuchs; Valérie Gailus-Durner; Martin Hrabe de Angelis; Dan Ehninger
Journal:  J Clin Invest       Date:  2013-07-25       Impact factor: 14.808

7.  Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival.

Authors:  Fresnida J Ramos; Steven C Chen; Michael G Garelick; Dao-Fu Dai; Chen-Yu Liao; Katherine H Schreiber; Vivian L MacKay; Elroy H An; Randy Strong; Warren C Ladiges; Peter S Rabinovitch; Matt Kaeberlein; Brian K Kennedy
Journal:  Sci Transl Med       Date:  2012-07-25       Impact factor: 17.956

8.  Rapamycin slows aging in mice.

Authors:  John E Wilkinson; Lisa Burmeister; Susan V Brooks; Chi-Chao Chan; Sabrina Friedline; David E Harrison; James F Hejtmancik; Nancy Nadon; Randy Strong; Lauren K Wood; Maria A Woodward; Richard A Miller
Journal:  Aging Cell       Date:  2012-06-04       Impact factor: 9.304

9.  Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system.

Authors:  Sebastian I Arriola Apelo; Joshua C Neuman; Emma L Baar; Faizan A Syed; Nicole E Cummings; Harpreet K Brar; Cassidy P Pumper; Michelle E Kimple; Dudley W Lamming
Journal:  Aging Cell       Date:  2015-10-13       Impact factor: 9.304

10.  Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan.

Authors:  Dudley W Lamming; Maria M Mihaylova; Pekka Katajisto; Emma L Baar; Omer H Yilmaz; Amanda Hutchins; Yetis Gultekin; Rachel Gaither; David M Sabatini
Journal:  Aging Cell       Date:  2014-07-25       Impact factor: 9.304

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  55 in total

Review 1.  Key proteins and pathways that regulate lifespan.

Authors:  Haihui Pan; Toren Finkel
Journal:  J Biol Chem       Date:  2017-03-06       Impact factor: 5.157

Review 2.  Nutrition, metabolism, and targeting aging in nonhuman primates.

Authors:  Priya Balasubramanian; Julie A Mattison; Rozalyn M Anderson
Journal:  Ageing Res Rev       Date:  2017-02-20       Impact factor: 10.895

Review 3.  The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging.

Authors:  Brian K Kennedy; Dudley W Lamming
Journal:  Cell Metab       Date:  2016-06-14       Impact factor: 27.287

4.  Long-term treatment with the mTOR inhibitor rapamycin has minor effect on clinical laboratory markers in middle-aged marmosets.

Authors:  Aubrey M Sills; Joselyn M Artavia; Brian D DeRosa; Corinna N Ross; Adam B Salmon
Journal:  Am J Primatol       Date:  2018-10-12       Impact factor: 2.371

5.  A toolbox for the longitudinal assessment of healthspan in aging mice.

Authors:  I Bellantuono; R de Cabo; D Ehninger; C Di Germanio; A Lawrie; J Miller; S J Mitchell; I Navas-Enamorado; P K Potter; T Tchkonia; J L Trejo; D W Lamming
Journal:  Nat Protoc       Date:  2020-01-08       Impact factor: 13.491

Review 6.  Next Generation Strategies for Geroprotection via mTORC1 Inhibition.

Authors:  Sabrina N Dumas; Dudley W Lamming
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2020-01-01       Impact factor: 6.053

Review 7.  Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island.

Authors:  Sebastian I Arriola Apelo; Dudley W Lamming
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2016-05-21       Impact factor: 6.053

Review 8.  β-Cell Autophagy in Diabetes Pathogenesis.

Authors:  Michelle R Marasco; Amelia K Linnemann
Journal:  Endocrinology       Date:  2018-05-01       Impact factor: 4.736

Review 9.  Lysosome: The metabolic signaling hub.

Authors:  Dudley W Lamming; Liron Bar-Peled
Journal:  Traffic       Date:  2018-11-14       Impact factor: 6.215

Review 10.  mTOR at the nexus of nutrition, growth, ageing and disease.

Authors:  Grace Y Liu; David M Sabatini
Journal:  Nat Rev Mol Cell Biol       Date:  2020-01-14       Impact factor: 94.444

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