DISCOVERIES (ISSN 2359-7232), 2015, October-December issue
Submitted: December 27th, 2015; Accepted: December 30th, 2015; Published: December 31st, 2015;
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AMPK activation can delay aging
Andreea Lucia Stancu *
Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA
*Correspondence to: Andreea L. Stancu, MD, Department of Pathology, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA. E-mail: astancu@bidmc.harvard.edu
Abstract
AMPK controls the regulation of cellular homeostasis, metabolism, resistance to stress, cell survival and growth, cell death, autophagy, which are some of the most critical determinants of aging and lifespan. Specific AMPK activation was recently shown to delay aging and prolong lifespan in Drosophila melanogaster. Indirect AMPK activators, such as resveratrol, metformin and exercise, are currently in clinical trials for studying their impact on human aging-related characteristics, tissue homeostasis and metabolic dysfunctions. In this minireview, I am briefly discussing the recent advances on AMP involvement in aging and lifespan elongation.
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References
1. Hardie DG. Regulation of AMP-activated protein kinase by natural and synthetic activator. Acta Pharmaceutica Sinica B; available online on 21 July 2015.
View article (DOI)2. García-Prieto CF, Pulido-Olmo H, Ruiz-Hurtado G, Gil-Ortega M, Aranguez I, Rubio MA. Mild caloric restriction reduces blood pressure and activates endothelial AMPK-PI3K-Akt-eNOS pathway in obese Zucker rats. Vascul Pharmacol. 2015 Feb-Mar;65-66:3-12. doi: 10.1016/j.vph.2014.12.001.; PMID: 25530153.2. Ruderman NB, Xu XJ, Nelson L, Cacicedo JM, Saha AK, Lan F, Ido Y. AMPK and SIRT1: a long-standing partnership? Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E751-60.
View article (DOI) PubMed
3. Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev. 2012 Apr;11(2):230-41.
View article (DOI) PubMed
4. Ning YC, Cai GY, Zhuo L, Gao JJ, Dong D, Cui S et al. Short-term calorie restriction protects against renal senescence of aged rats by increasing autophagic activity and reducing oxidative damage. Mech Ageing Dev. 2013; 134(11-12): 570-9.
View article (DOI) PubMed
6. Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D et al. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol. 2007 Oct 9;17(19):1646-56. PMID: 17900900.
View article (DOI) PubMed
7. Greer EL, Banko MR, Brunet A. AMP-activated protein kinase and FoxO transcription factors in dietary restriction-induced longevity. Ann N Y Acad Sci. 2009 Jul;1170:688-92.
View article (DOI) PubMed
8. Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene. 2005 Nov 14;24(50):7410-25.
View article (DOI) PubMed
9. Chen S, Zhou N, Zhang Z, Li W, Zhu W. Resveratrol induces cell apoptosis in adipocytes via AMPK activation. Biochem Biophys Res Commun. 2015 Feb 20; 457(4): 608-13. doi: 10.1016/j.bbrc.2015.01.034.
View article (DOI) PubMed
10. Chen S, Li Z, Li W, Shan Z, Zhu W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can J Physiol Pharmacol. 2011 Nov;89(11):793-9.
View article (DOI) PubMed
11. Chen S, Xiao X, Feng X, Li W, Zhou N, Zheng L. Resveratrol induces Sirt1-dependent apoptosis in 3T3-L1 preadipocytes by activating AMPK and suppressing AKT activity and survivin expression. J Nutr Biochem. 2012 Sep;23(9):1100-12.
View article (DOI) PubMed
12. Duca FA, Côté CD, Rasmussen BA, Zadeh-Tahmasebi M, Rutter GA, Filippi BM. Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats. Nat Med. 2015 May;21(5):506-11.
View article (DOI) PubMed
13. Fentz J, Kjøbsted R, Kristensen CM, Hingst JR, Birk JB, Gudiksen A. AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2015 Dec 1; 309(11): E900-14.
View article (DOI) PubMed
14. Lundberg TR, Fernandez-Gonzalo R, Tesch PA. Exercise-induced AMPK activation does not interfere with muscle hypertrophy in response to resistance training in men. J Appl Physiol (1985). 2014 Mar 15; 116(6): 611-20.
View article (DOI) PubMed
15. ClinicalTrials.gov; accessed in December 2015:
https://clinicaltrials.gov/ct2/results?term=AMPK%2C+aging&Search=Search
16. ClinicalTrials.gov registry of U.S. NIH; NCT01793896; accessed in December 2015:
https://clinicaltrials.gov/ct2/show/NCT01793896
17. ClinicalTrials.gov registry of U.S. NIH; NCT01737164; accessed in December 2015:
https://clinicaltrials.gov/ct2/show/NCT01737164
18. ClinicalTrials.gov registry of U.S. NIH; NCT01765946; accessed in December 2015:
https://clinicaltrials.gov/ct2/show/NCT01765946
19. ClinicalTrials.gov registry of U.S. NIH; NCT02432287; accessed in December 2015:
https://clinicaltrials.gov/ct2/show/NCT02432287
20. ClinicalTrials.gov registry of U.S. NIH; NCT02123121; accessed in December 2015:
https://clinicaltrials.gov/ct2/show/NCT02123121
21. Ulgherait M, Rana A, Rera M, Graniel J, Walker DW. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Rep. 2014 Sep 25;8(6):1767-80. doi: . PMID: 25199830.
View article (DOI) PubMed
22. Senesi P, Montesano A, Luzi L, Codella R, Benedini S, Terruzzi I. Metformin Treatment Prevents Sedentariness Related Damages in Mice. J Diabetes Res. 2016; 2016: 8274689.
View article (DOI) PubMed
23. Dumitrascu GR, Bucur O. Critical physiological and pathological functions of Forkhead Box O tumor suppressors. Discoveries 2013, Oct-Dec; 1(1): e5.
View article (DOI)
24. Plati J, Bucur O, Khosravi-Far R. Dysregulation of apoptotic signaling in cancer: molecular mechanisms and therapeutic opportunities. J Cell Biochem. 2008 Jul 1; 104(4): 1124-49.
View article (DOI) PubMed
25. Singh A, Ye M, Bucur O, Zhu S, Tanya Santos M, Rabinovitz I et al. Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT. Mol Biol Cell. 2010 Mar 15; 21(6): 1140-52.
View article (DOI) PubMed
26. Wang Y, Liang Y, Vanhoutte PM. SIRT1 and AMPK in regulating mammalian senescence: a critical review and a working model. FEBS Lett. 2011 Apr 6;585(7):986-94.
View article (DOI) PubMed
27. Pirkmajer S, Kulkarni SS, Tom RZ, Ross FA, Hawley SA, Hardie DG et al. Methotrexate promotes glucose uptake and lipid oxidation in skeletal muscle via AMPK activation. Diabetes. 2015 Feb;64(2):360-9.
View article (DOI) PubMed
28. Anwar MA, Kheir WA, Eid S, Fares J, Liu X, Eid AH, Eid AA.. Colorectal and Prostate Cancer Risk in Diabetes: Metformin, an Actor behind the Scene. J Cancer. 2014 Oct 9;5(9):736-44.
View article (DOI) PubMed
29. Bhat A, Sebastiani G, Bhat M. Systematic review: Preventive and therapeutic applications of metformin in liver disease. World J Hepatol. 2015 Jun 28;7(12):1652-9.
View article (DOI) PubMed
30. Na HJ, Park JS, Pyo JH, Jeon HJ, Kim YS, Arking R, Yoo MA. Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway. Mech Ageing Dev. 2015 Jul;149:8-18.
View article (DOI) PubMed
31. Na HJ, Park JS, Pyo JH, Lee SH, Jeon HJ, Kim YS, Yoo MA. Mechanism of metformin: inhibition of DNA damage and proliferative activity in Drosophila midgut stem cell. Mech Ageing Dev. 2013 Sep; 134(9): 381-90.
View article (DOI) PubMed
32. Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M. Metformin improves healthspan and lifespan in mice. Nat Commun. 2013;4:2192.
View article (DOI) PubMed
33. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009 Jul 16;460(7253):392-5.
View article (DOI) PubMed
34. Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010 Jan;11(1):35-46.
View article (DOI) PubMed
35. Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011 Sep 2;146(5):682-95.
View article (DOI) PubMed
36. Bucur O, Ray S, Bucur MC, Almasan A. APO2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in prostate cancer therapy. Front Biosci. 2006 May 1;11:1549-68.
View article (DOI) PubMed
37. Burkewitz K, Zhang Y, Mair WB. AMPK at the nexus of energetics and aging. Cell Metab. 2014 Jul 1;20(1):10-25.
View article (DOI) PubMed
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