Literature DB >> 23454761

Rapalogs and mTOR inhibitors as anti-aging therapeutics.

Dudley W Lamming1, Lan Ye, David M Sabatini, Joseph A Baur.   

Abstract

Rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has the strongest experimental support to date as a potential anti-aging therapeutic in mammals. Unlike many other compounds that have been claimed to influence longevity, rapamycin has been repeatedly tested in long-lived, genetically heterogeneous mice, in which it extends both mean and maximum life spans. However, the mechanism that accounts for these effects is far from clear, and a growing list of side effects make it doubtful that rapamycin would ultimately be beneficial in humans. This Review discusses the prospects for developing newer, safer anti-aging therapies based on analogs of rapamycin (termed rapalogs) or other approaches targeting mTOR signaling.

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Year:  2013        PMID: 23454761      PMCID: PMC3582126          DOI: 10.1172/JCI64099

Source DB:  PubMed          Journal:  J Clin Invest        ISSN: 0021-9738            Impact factor:   14.808


  130 in total

1.  Premature aging in mice activates a systemic metabolic response involving autophagy induction.

Authors:  Guillermo Mariño; Alejandro P Ugalde; Natalia Salvador-Montoliu; Ignacio Varela; Pedro M Quirós; Juan Cadiñanos; Ingrid van der Pluijm; José M P Freije; Carlos López-Otín
Journal:  Hum Mol Genet       Date:  2008-04-28       Impact factor: 6.150

2.  Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k.

Authors:  H B Jefferies; S Fumagalli; P B Dennis; C Reinhard; R B Pearson; G Thomas
Journal:  EMBO J       Date:  1997-06-16       Impact factor: 11.598

3.  Distinct repression of translation by wortmannin and rapamycin.

Authors:  S Pedersen; J E Celis; J Nielsen; J Christiansen; F C Nielsen
Journal:  Eur J Biochem       Date:  1997-07-01

4.  Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function.

Authors:  Cong Zhang; Ana Maria Cuervo
Journal:  Nat Med       Date:  2008-09       Impact factor: 53.440

Review 5.  Drug discovery approaches targeting the PI3K/Akt pathway in cancer.

Authors:  C Garcia-Echeverria; W R Sellers
Journal:  Oncogene       Date:  2008-09-18       Impact factor: 9.867

6.  AMPK phosphorylation of raptor mediates a metabolic checkpoint.

Authors:  Dana M Gwinn; David B Shackelford; Daniel F Egan; Maria M Mihaylova; Annabelle Mery; Debbie S Vasquez; Benjamin E Turk; Reuben J Shaw
Journal:  Mol Cell       Date:  2008-04-25       Impact factor: 17.970

7.  Sirolimus may reduce fertility in male renal transplant recipients.

Authors:  J Zuber; D Anglicheau; C Elie; L Bererhi; M-O Timsit; M-F Mamzer-Bruneel; M Ciroldi; F Martinez; R Snanoudj; C Hiesse; H Kreis; F Eustache; K Laborde; E Thervet; C Legendre
Journal:  Am J Transplant       Date:  2008-07       Impact factor: 8.086

8.  Caffeine extends yeast lifespan by targeting TORC1.

Authors:  Valeria Wanke; Elisabetta Cameroni; Aino Uotila; Manuele Piccolis; Jörg Urban; Robbie Loewith; Claudio De Virgilio
Journal:  Mol Microbiol       Date:  2008-05-26       Impact factor: 3.501

9.  Metformin slows down aging and extends life span of female SHR mice.

Authors:  Vladimir N Anisimov; Lev M Berstein; Peter A Egormin; Tatiana S Piskunova; Irina G Popovich; Mark A Zabezhinski; Margarita L Tyndyk; Maria V Yurova; Irina G Kovalenko; Tatiana E Poroshina; Anna V Semenchenko
Journal:  Cell Cycle       Date:  2008-09-11       Impact factor: 4.534

10.  A role for autophagy in the extension of lifespan by dietary restriction in C. elegans.

Authors:  Malene Hansen; Abha Chandra; Laura L Mitic; Brian Onken; Monica Driscoll; Cynthia Kenyon
Journal:  PLoS Genet       Date:  2008-02       Impact factor: 5.917

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  199 in total

1.  AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects.

Authors:  Diána Papp; Tibor Kovács; Viktor Billes; Máté Varga; Anna Tarnóci; László Hackler; László G Puskás; Hanna Liliom; Krisztián Tárnok; Katalin Schlett; Adrienn Borsy; Zsolt Pádár; Attila L Kovács; Krisztina Hegedűs; Gábor Juhász; Marcell Komlós; Attila Erdős; Balázs Gulyás; Tibor Vellai
Journal:  Autophagy       Date:  2016       Impact factor: 16.016

Review 2.  mTOR in health and in sickness.

Authors:  Dritan Liko; Michael N Hall
Journal:  J Mol Med (Berl)       Date:  2015-09-22       Impact factor: 4.599

Review 3.  Strategies for Achieving Healthy Vascular Aging.

Authors:  Kristen L Nowak; Matthew J Rossman; Michel Chonchol; Douglas R Seals
Journal:  Hypertension       Date:  2018-01-08       Impact factor: 10.190

4.  Effect of Metformin, Rapamycin, and Their Combination on Growth and Progression of Prostate Tumors in HiMyc Mice.

Authors:  Achinto Saha; Jorge Blando; Lisa Tremmel; John DiGiovanni
Journal:  Cancer Prev Res (Phila)       Date:  2015-04-23

5.  Continuous administration of the mTORC1 inhibitor everolimus induces tolerance and decreases autophagy in mice.

Authors:  Ammar Kurdi; Mireille De Doncker; Arthur Leloup; Hugo Neels; Jean-Pierre Timmermans; Katrien Lemmens; Sandra Apers; Guido R Y De Meyer; Wim Martinet
Journal:  Br J Pharmacol       Date:  2016-10-23       Impact factor: 8.739

Review 6.  mTOR: a pharmacologic target for autophagy regulation.

Authors:  Young Chul Kim; Kun-Liang Guan
Journal:  J Clin Invest       Date:  2015-01-02       Impact factor: 14.808

7.  mTOR inhibitors blunt the p53 response to nucleolar stress by regulating RPL11 and MDM2 levels.

Authors:  Kaveh M Goudarzi; Monica Nistér; Mikael S Lindström
Journal:  Cancer Biol Ther       Date:  2014       Impact factor: 4.742

8.  Coming of age: molecular drivers of aging and therapeutic opportunities.

Authors:  Christopher B Newgard; Norman E Sharpless
Journal:  J Clin Invest       Date:  2013-03-01       Impact factor: 14.808

9.  Immune-Stimulatory Effects of Rapamycin Are Mediated by Stimulation of Antitumor γδ T Cells.

Authors:  Vinh Dao; Yang Liu; Srilakshmi Pandeswara; Robert S Svatek; Jonathan A Gelfond; Aijie Liu; Vincent Hurez; Tyler J Curiel
Journal:  Cancer Res       Date:  2016-08-28       Impact factor: 12.701

10.  AMP-activated protein kinase deficiency rescues paraquat-induced cardiac contractile dysfunction through an autophagy-dependent mechanism.

Authors:  Qiurong Wang; Lifang Yang; Yinan Hua; Sreejayan Nair; Xihui Xu; Jun Ren
Journal:  Toxicol Sci       Date:  2014-08-04       Impact factor: 4.849

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