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Autophagy Induction: A Promising Antiaging Strategy

  • Abhishek Kumar Singh
  • Sandeep Singh
  • Syed Ibrahim Rizvi
Chapter

Abstract

Aging is a multifactorial biological phenomenon manifested by oxidative damage of biomolecules and cell organelles and their continuous accumulation, resulting in progressive loss of physiological functionality and high risk of mortality. Efforts to develop strategies for extending health span and lifespan are now in spotlight of geroscience. There are several studies suggesting the involvement of autophagy in aging. Autophagy is a conserved and protective intracellular lysosomal degradation process that ensures continuous removal and recycling of accumulated biomolecules and nonfunctional cell organelles to maintain cellular homeostasis and overall functionality of the cells. The age-dependent defective autophagy has also been suggested to further accelerate aging and increase the risk of other aging-related diseases. In addition, autophagy integrates several pro-survival pathway(s) as associated with AMP kinase (AMPK) and mammalian target of rapamycin (mTOR) to regulate growth, division, motility and overall survival of the cells. The pharmacological modulators of autophagy have been found rewarding in case of aging, and thus it is promising to expect autophagy modulators to be the next-generation antiaging drugs. This chapter summarizes the existing advances, perspectives, and challenges in the area of antiaging through induction of autophagy.

Keywords

Aging AMPK Autophagy mTOR Oxidative stress Sirtuins 

Notes

Acknowledgements

A. K. Singh would like to thank University Grants Commission, New Delhi, India, for providing Dr. D. S. Kothari postdoctoral fellowship and financial support (F.4-2/2006(BSR)/BL/14-15/0326). The Department of Biochemistry, University of Allahabad, is supported by the FIST grant from the DST-SERB and SAP-DRS I from University Grants Commission, Government of India.

References

  1. Anderson RM, Weindruch R (2012) The caloric restriction paradigm: implications for healthy human aging. Am J Hum Biol Off J Hum Biol Counc 24:101–106.  https://doi.org/10.1002/ajhb.22243 CrossRefGoogle Scholar
  2. Axe EL, Walker SA, Manifava M et al (2008) Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 182:685–701.  https://doi.org/10.1083/jcb.200803137 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bandyopadhyay U, Cuervo AM (2008) Entering the lysosome through a transient gate by chaperone-mediated autophagy. Autophagy 4:1101–1103CrossRefGoogle Scholar
  4. Barlow AD, Thomas DC (2015) Autophagy in diabetes: β-cell dysfunction, insulin resistance, and complications. DNA Cell Biol 34:252–260.  https://doi.org/10.1089/dna.2014.2755 CrossRefPubMedGoogle Scholar
  5. Bejarano E, Cuervo AM (2010) Chaperone-mediated autophagy. Proc Am Thorac Soc 7:29–39.  https://doi.org/10.1513/pats.200909-102JS CrossRefPubMedPubMedCentralGoogle Scholar
  6. Blagosklonny MV (2013) Rapamycin extends life- and health span because it slows aging. Aging 5:592–598.  https://doi.org/10.18632/aging.100591 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Brenmoehl J, Hoeflich A (2013) Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3. Mitochondrion 13:755–761.  https://doi.org/10.1016/j.mito.2013.04.002 CrossRefPubMedGoogle Scholar
  8. Burkewitz K, Zhang Y, Mair WB (2014) AMPK at the Nexus of energetics and aging. Cell Metab 20:10–25.  https://doi.org/10.1016/j.cmet.2014.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cai Z, Yan LJ (2013) Rapamycin, autophagy, and Alzheimer’s disease. J Biochem Pharmacol Res 1:84–90PubMedPubMedCentralGoogle Scholar
  10. Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ (2009) Vitagenes, cellular stress response, and acetylcarnitine: relevance to hormesis. BioFactors Oxf Engl 35:146–160.  https://doi.org/10.1002/biof.22 CrossRefGoogle Scholar
  11. Calabrese V, Cornelius C, Mancuso C et al (2010) Redox homeostasis and cellular stress response in aging and neurodegeneration. Methods Mol Biol Clifton NJ 610:285–308.  https://doi.org/10.1007/978-1-60327-029-8_17 CrossRefGoogle Scholar
  12. Cuervo AM, Dice JF (2000) Regulation of lamp2a levels in the lysosomal membrane. Traffic Cph Den 1:570–583CrossRefGoogle Scholar
  13. Choi SI, Kim B-Y, Dadakhujaev S et al (2012) Impaired autophagy and delayed autophagic clearance of transforming growth factor β-induced protein (TGFBI) in granular corneal dystrophy type 2. Autophagy 8:1782–1797.  https://doi.org/10.4161/auto.22067 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Cuervo AM, Bergamini E, Brunk UT et al (2005) Autophagy and aging: the importance of maintaining “clean” cells. Autophagy 1:131–140CrossRefGoogle Scholar
  15. Del Roso A, Vittorini S, Cavallini G et al (2003) Ageing-related changes in the in vivo function of rat liver macroautophagy and proteolysis. Exp Gerontol 38:519–527CrossRefGoogle Scholar
  16. Dutta D, Xu J, Dirain MLS, Leeuwenburgh C (2014) Calorie restriction combined with resveratrol induces autophagy and protects 26-month-old rat hearts from doxorubicin-induced toxicity. Free Radic Biol Med 74:252–262.  https://doi.org/10.1016/j.freeradbiomed.2014.06.011 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Ebato C, Uchida T, Arakawa M et al (2008) Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 8:325–332.  https://doi.org/10.1016/j.cmet.2008.08.009 CrossRefPubMedGoogle Scholar
  18. Ehninger D, Neff F, Xie K (2014) Longevity, aging and rapamycin. Cell Mol Life Sci 71:4325–4346.  https://doi.org/10.1007/s00018-014-1677-1 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Eisenberg-Lerner A, Kimchi A (2012) PKD at the crossroads of necrosis and autophagy. Autophagy 8:433–434.  https://doi.org/10.4161/auto.19288 CrossRefPubMedGoogle Scholar
  20. Fang EF, Scheibye-Knudsen M, Chua KF et al (2016) Nuclear DNA damage signalling to mitochondria in ageing. Nat Rev Mol Cell Biol 17:308–321.  https://doi.org/10.1038/nrm.2016.14 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247.  https://doi.org/10.1038/35041687 CrossRefPubMedGoogle Scholar
  22. Fleming A, Noda T, Yoshimori T, Rubinsztein DC (2011) Chemical modulators of autophagy as biological probes and potential therapeutics. Nat Chem Biol 7:9–17.  https://doi.org/10.1038/nchembio.500 CrossRefPubMedGoogle Scholar
  23. Floyd RA, Hensley K (2002) Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 23:795–807CrossRefGoogle Scholar
  24. Fusco D, Colloca G, Lo Monaco MR, Cesari M (2007) Effects of antioxidant supplementation on the aging process. Clin Interv Aging 2:377–387PubMedPubMedCentralGoogle Scholar
  25. Garg G, Singh S, Singh AK, Rizvi SI (2017) Antiaging effect of metformin on brain in naturally aged and accelerated senescence model of rat. Rejuvenation Res 20:173–182.  https://doi.org/10.1089/rej.2016.1883 CrossRefPubMedGoogle Scholar
  26. Glick D, Barth S, Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221:3–12.  https://doi.org/10.1002/path.2697 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Grotemeier A, Alers S, Pfisterer SG et al (2010) AMPK-independent induction of autophagy by cytosolic Ca2+ increase. Cell Signal 22:914–925.  https://doi.org/10.1016/j.cellsig.2010.01.015 CrossRefPubMedGoogle Scholar
  28. Hailey DW, Rambold AS, Satpute-Krishnan P et al (2010) Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 141:656–667.  https://doi.org/10.1016/j.cell.2010.04.009 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet Lond Engl 344:721–724CrossRefGoogle Scholar
  30. Handschin C (2016) Caloric restriction and exercise “mimetics”: ready for prime time? Pharmacol Res 103:158–166.  https://doi.org/10.1016/j.phrs.2015.11.009 CrossRefPubMedGoogle Scholar
  31. Hara K, Maruki Y, Long X et al (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110:177–189CrossRefGoogle Scholar
  32. Hariharan N, Maejima Y, Nakae J et al (2010) Deacetylation of FoxO by Sirt1 plays an essential role in mediating starvation-induced autophagy in cardiac myocytes. Circ Res 107:1470–1482.  https://doi.org/10.1161/CIRCRESAHA.110.227371 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300CrossRefGoogle Scholar
  34. Harman D (1981) The aging process. Proc Natl Acad Sci U S A 78:7124–7128CrossRefGoogle Scholar
  35. Harman D (2003) The free radical theory of aging. Antioxid Redox Signal 5:557–561.  https://doi.org/10.1089/152308603770310202 CrossRefPubMedGoogle Scholar
  36. Harris J (2011) Autophagy and cytokines. Cytokine 56:140–144.  https://doi.org/10.1016/j.cyto.2011.08.022 CrossRefPubMedGoogle Scholar
  37. He L-q, Lu J-h, Yue Z-y (2013) Autophagy in ageing and ageing-associated diseases. Acta Pharmacol Sin 34:605–611.  https://doi.org/10.1038/aps.2012.188 CrossRefGoogle Scholar
  38. Hoshino A, Mita Y, Okawa Y et al (2013) Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart. Nat Commun 4:2308.  https://doi.org/10.1038/ncomms3308 CrossRefPubMedGoogle Scholar
  39. Ingram DK, Roth GS (2015) Calorie restriction mimetics: can you have your cake and eat it, too? Ageing Res Rev 20:46–62.  https://doi.org/10.1016/j.arr.2014.11.005 CrossRefPubMedGoogle Scholar
  40. Ingram DK, Anson RM, Cabo R et al (2004) Development of calorie restriction mimetics as a prolongevity strategy. Ann N Y Acad Sci 1019:412–423.  https://doi.org/10.1196/annals.1297.074 CrossRefPubMedGoogle Scholar
  41. Jacinto E, Loewith R, Schmidt A et al (2004) Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6:1122–1128.  https://doi.org/10.1038/ncb1183 CrossRefPubMedGoogle Scholar
  42. Jiang P, Mizushima N (2014) Autophagy and human diseases. Cell Res 24:69–79.  https://doi.org/10.1038/cr.2013.161 CrossRefPubMedGoogle Scholar
  43. Jung HS, Chung KW, Won Kim J et al (2008) Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab 8:318–324.  https://doi.org/10.1016/j.cmet.2008.08.013 CrossRefPubMedGoogle Scholar
  44. Kaeberlein M (2010) Resveratrol and rapamycin: are they anti-aging drugs? BioEssays 32:96–99.  https://doi.org/10.1002/bies.200900171 CrossRefPubMedGoogle Scholar
  45. Kaniuk NA, Kiraly M, Bates H et al (2007) Ubiquitinated-protein aggregates form in pancreatic beta-cells during diabetes-induced oxidative stress and are regulated by autophagy. Diabetes 56:930–939.  https://doi.org/10.2337/db06-1160 CrossRefPubMedGoogle Scholar
  46. Kaushik S, Cuervo AM (2015) Proteostasis and aging. Nat Med 21:1406–1415.  https://doi.org/10.1038/nm.4001 CrossRefPubMedGoogle Scholar
  47. Kennedy BK, Berger SL, Brunet A et al (2014) Geroscience: linking aging to chronic disease. Cell 159:709–713.  https://doi.org/10.1016/j.cell.2014.10.039 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Kibe R, Kurihara S, Sakai Y et al (2014) Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice. Sci Rep 4:4548.  https://doi.org/10.1038/srep04548 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Kiffin R (2004) Activation of chaperone-mediated autophagy during oxidative stress. Mol Biol Cell 15:4829–4840.  https://doi.org/10.1091/mbc.E04-06-0477 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Kim DH, Sarbassov DD, Ali SM et al (2003) GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 11:895–904CrossRefGoogle Scholar
  51. Kim J, Kundu M, Viollet B, Guan K-L (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13:132–141.  https://doi.org/10.1038/ncb2152 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Kirkwood TBL (2005) Understanding the odd science of aging. Cell 120:437–447.  https://doi.org/10.1016/j.cell.2005.01.027 CrossRefPubMedGoogle Scholar
  53. Klionsky DJ (2007) Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 8:931–937.  https://doi.org/10.1038/nrm2245 CrossRefPubMedGoogle Scholar
  54. Kobayashi S (2015) Choose delicately and reuse adequately: the newly revealed process of autophagy. Biol Pharm Bull 38:1098–1103.  https://doi.org/10.1248/bpb.b15-00096 CrossRefPubMedGoogle Scholar
  55. Korovila I, Hugo M, Castro JP et al (2017) Proteostasis, oxidative stress and aging. Redox Biol 13:550–567.  https://doi.org/10.1016/j.redox.2017.07.008 CrossRefPubMedPubMedCentralGoogle Scholar
  56. Kosacka J, Kern M, Klöting N et al (2015) Autophagy in adipose tissue of patients with obesity and type 2 diabetes. Mol Cell Endocrinol 409:21–32.  https://doi.org/10.1016/j.mce.2015.03.015 CrossRefPubMedGoogle Scholar
  57. Lapierre LR, De Magalhaes Filho CD, McQuary PR et al (2013) The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun 4:2267.  https://doi.org/10.1038/ncomms3267 CrossRefPubMedGoogle Scholar
  58. Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42.  https://doi.org/10.1016/j.cell.2007.12.018 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Li Q, Liu Y, Sun M (2017) Autophagy and Alzheimer’s disease. Cell Mol Neurobiol 37:377–388.  https://doi.org/10.1007/s10571-016-0386-8 CrossRefPubMedGoogle Scholar
  60. Lipinski MM, Zheng B, Lu T et al (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci U S A 107:14164–14169.  https://doi.org/10.1073/pnas.1009485107 CrossRefPubMedPubMedCentralGoogle Scholar
  61. López-Lluch G, Navas P (2016) Calorie restriction as an intervention in ageing. J Physiol 594:2043–2060.  https://doi.org/10.1113/JP270543 CrossRefPubMedPubMedCentralGoogle Scholar
  62. López-Otín C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217.  https://doi.org/10.1016/j.cell.2013.05.039 CrossRefPubMedPubMedCentralGoogle Scholar
  63. López-Otín C, Galluzzi L, Freije JMP et al (2016) Metabolic control of longevity. Cell 166:802–821.  https://doi.org/10.1016/j.cell.2016.07.031 CrossRefPubMedGoogle Scholar
  64. Madeo F, Pietrocola F, Eisenberg T, Kroemer G (2014) Caloric restriction mimetics: towards a molecular definition. Nat Rev Drug Discov 13:727–740.  https://doi.org/10.1038/nrd4391 CrossRefPubMedGoogle Scholar
  65. Mai S, Muster B, Bereiter-Hahn J, Jendrach M (2012) Autophagy proteins LC3B, ATG5 and ATG12 participate in quality control after mitochondrial damage and influence lifespan. Autophagy 8:47–62.  https://doi.org/10.4161/auto.8.1.18174 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Marchal J, Pifferi F, Aujard F (2013) Resveratrol in mammals: effects on aging biomarkers, age-related diseases, and life span. Ann N Y Acad Sci 1290:67–73.  https://doi.org/10.1111/nyas.12214 CrossRefPubMedGoogle Scholar
  67. Mariño G, Pietrocola F, Madeo F, Kroemer G (2014) Caloric restriction mimetics: natural/physiological pharmacological autophagy inducers. Autophagy 10:1879–1882.  https://doi.org/10.4161/auto.36413 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Marsh BJ, Soden C, Alarcón C et al (2007) Regulated autophagy controls hormone content in secretory-deficient pancreatic endocrine beta-cells. Mol Endocrinol Baltim Md 21:2255–2269.  https://doi.org/10.1210/me.2007-0077 CrossRefGoogle Scholar
  69. Martin-Montalvo A, de Cabo R (2013) Mitochondrial metabolic reprogramming induced by calorie restriction. Antioxid Redox Signal 19:310–320.  https://doi.org/10.1089/ars.2012.4866 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Mazucanti CH, Cabral-Costa JV, Vasconcelos AR et al (2015) Longevity pathways (mTOR, SIRT, insulin/IGF-1) as key modulatory targets on aging and neurodegeneration. Curr Top Med Chem 15:2116–2138CrossRefGoogle Scholar
  71. Mei Y, Thompson MD, Cohen RA, Tong X (2015) Autophagy and oxidative stress in cardiovascular diseases. Biochim Biophys Acta (BBA) – Mol Basis Dis 1852:243–251.  https://doi.org/10.1016/j.bbadis.2014.05.005 CrossRefGoogle Scholar
  72. Meléndez A, Tallóczy Z, Seaman M et al (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301:1387–1391.  https://doi.org/10.1126/science.1087782 CrossRefPubMedGoogle Scholar
  73. Mijaljica D, Prescott M, Devenish RJ (2011) Microautophagy in mammalian cells: revisiting a 40-year-old conundrum. Autophagy 7:673–682.  https://doi.org/10.4161/auto.7.7.14733 CrossRefPubMedGoogle Scholar
  74. Minois N (2014) Molecular basis of the “anti-aging” effect of spermidine and other natural polyamines – a mini-review. Gerontology 60:319–326.  https://doi.org/10.1159/000356748 CrossRefPubMedGoogle Scholar
  75. Morimoto RI, Cuervo AM (2014) Proteostasis and the aging proteome in health and disease. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S33–S38.  https://doi.org/10.1093/gerona/glu049 CrossRefPubMedPubMedCentralGoogle Scholar
  76. Morselli E, Galluzzi L, Kepp O et al (2009) Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol. Aging 1:961–970.  https://doi.org/10.18632/aging.100110 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Mouchiroud L, Molin L, Dallière N, Solari F (2010) Life span extension by resveratrol, rapamycin, and metformin: the promise of dietary restriction mimetics for an healthy aging. Biofactors 36:377–382.  https://doi.org/10.1002/biof.127 CrossRefPubMedGoogle Scholar
  78. Ng F, Tang BL (2013) Sirtuins’ modulation of autophagy. J Cell Physiol 228:2262–2270.  https://doi.org/10.1002/jcp.24399 CrossRefPubMedGoogle Scholar
  79. Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol CB 22:R741–R752.  https://doi.org/10.1016/j.cub.2012.07.024 CrossRefPubMedGoogle Scholar
  80. Niu Y, Na L, Feng R et al (2013) The phytochemical, EGCG, extends lifespan by reducing liver and kidney function damage and improving age-associated inflammation and oxidative stress in healthy rats. Aging Cell 12:1041–1049.  https://doi.org/10.1111/acel.12133 CrossRefPubMedGoogle Scholar
  81. Nixon RA, Yang DS (2011) Autophagy failure in Alzheimer’s disease – locating the primary defect. Neurobiol Dis 43:38–45.  https://doi.org/10.1016/j.nbd.2011.01.021 CrossRefPubMedPubMedCentralGoogle Scholar
  82. Ohsumi Y (2014) Historical landmarks of autophagy research. Cell Res 24:9–23.  https://doi.org/10.1038/cr.2013.169 CrossRefPubMedGoogle Scholar
  83. Pearson KJ, Baur JA, Lewis KN et al (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157–168.  https://doi.org/10.1016/j.cmet.2008.06.011 CrossRefPubMedPubMedCentralGoogle Scholar
  84. Periyasamy-Thandavan S, Jiang M, Schoenlein P, Dong Z (2009) Autophagy: molecular machinery, regulation, and implications for renal pathophysiology. Am J Physiol Renal Physiol 297:F244–F256.  https://doi.org/10.1152/ajprenal.00033.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  85. Poli G, Leonarduzzi G, Biasi F, Chiarpotto E (2004) Oxidative stress and cell signalling. Curr Med Chem 11:1163–1182CrossRefGoogle Scholar
  86. Pyo JO, Yoo SM, Ahn HH et al (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4:2300.  https://doi.org/10.1038/ncomms3300 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Quan W, Lim YM, Lee MS (2012) Role of autophagy in diabetes and endoplasmic reticulum stress of pancreatic β-cells. Exp Mol Med 44:81–88.  https://doi.org/10.3858/emm.2012.44.2.030 CrossRefPubMedPubMedCentralGoogle Scholar
  88. Querfurth HW, LaFerla FM (2010) Alzheimer’s disease. N Engl J Med 362:329–344.  https://doi.org/10.1056/NEJMra0909142 CrossRefPubMedGoogle Scholar
  89. Ravikumar B, Sarkar S, Davies JE et al (2010) Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 90:1383–1435.  https://doi.org/10.1152/physrev.00030.2009 CrossRefPubMedGoogle Scholar
  90. Renna M, Bento CF, Fleming A et al (2013) IGF-1 receptor antagonism inhibits autophagy. Hum Mol Genet 22:4528–4544.  https://doi.org/10.1093/hmg/ddt300 CrossRefPubMedPubMedCentralGoogle Scholar
  91. Rodriguez M, Rodriguez-Sabate C, Morales I et al (2015) Parkinson’s disease as a result of aging. Aging Cell 14:293–308.  https://doi.org/10.1111/acel.12312 CrossRefPubMedPubMedCentralGoogle Scholar
  92. Rothermel BA, Hill JA (2007) Myocyte autophagy in heart disease: friend or foe? Autophagy 3:632–634CrossRefGoogle Scholar
  93. Rothermel BA, Hill JA (2008) Autophagy in load-induced heart disease. Circ Res 103:1363–1369.  https://doi.org/10.1161/CIRCRESAHA.108.186551 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Rubinsztein DC, Codogno P, Levine B (2012) Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 11:709–730.  https://doi.org/10.1038/nrd3802 CrossRefPubMedPubMedCentralGoogle Scholar
  95. Santini E, Klann E (2011) Dysregulated mTORC1-dependent translational control: from brain disorders to psychoactive drugs. Front Behav Neurosci 5:76.  https://doi.org/10.3389/fnbeh.2011.00076 CrossRefPubMedPubMedCentralGoogle Scholar
  96. Sarkar S (2013) Regulation of autophagy by mTOR-dependent and mTOR-independent pathways: autophagy dysfunction in neurodegenerative diseases and therapeutic application of autophagy enhancers. Biochem Soc Trans 41:1103–1130.  https://doi.org/10.1042/BST20130134 CrossRefPubMedGoogle Scholar
  97. Sciarretta S, Zhai P, Shao D et al (2012) Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome. Circulation 125:1134–1146.  https://doi.org/10.1161/CIRCULATIONAHA.111.078212 CrossRefPubMedPubMedCentralGoogle Scholar
  98. Shafei MA, Harris M, Conway ME (2017) Divergent metabolic regulation of autophagy and mTORC1-Early events in Alzheimer’s disease? Front Aging Neurosci 9:173.  https://doi.org/10.3389/fnagi.2017.00173 CrossRefPubMedPubMedCentralGoogle Scholar
  99. Shigenaga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A 91:10771–10778CrossRefGoogle Scholar
  100. Sies H (2015) Oxidative stress: a concept in redox biology and medicine. Redox Biol 4:180–183.  https://doi.org/10.1016/j.redox.2015.01.002 CrossRefPubMedPubMedCentralGoogle Scholar
  101. Singh AK, Kashyap MP, Tripathi VK et al (2017a) Neuroprotection through rapamycin-induced activation of autophagy and PI3K/Akt1/mTOR/CREB signaling against amyloid-β-induced oxidative stress, synaptic/neurotransmission dysfunction, and neurodegeneration in adult rats. Mol Neurobiol 54:5815–5828.  https://doi.org/10.1007/s12035-016-0129-3 CrossRefPubMedGoogle Scholar
  102. Singh S, Singh AK, Garg G, Rizvi SI (2017b) Fisetin as a caloric restriction mimetic protects rat brain against aging induced oxidative stress, apoptosis and neurodegeneration. Life Sci 193:171–179.  https://doi.org/10.1016/j.lfs.2017.11.004 CrossRefPubMedGoogle Scholar
  103. Spilman P, Podlutskaya N, Hart MJ et al (2010) Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer’s disease. PLoS One 5:e9979.  https://doi.org/10.1371/journal.pone.0009979 CrossRefPubMedPubMedCentralGoogle Scholar
  104. Taylor JP, Hardy J, Fischbeck KH (2002) Toxic proteins in neurodegenerative disease. Science 296:1991–1995.  https://doi.org/10.1126/science.1067122 CrossRefPubMedGoogle Scholar
  105. Testa G, Biasi F, Poli G, Chiarpotto E (2014) Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr Pharm Des 20:2950–2977CrossRefGoogle Scholar
  106. Texel SJ, Mattson MP (2011) Impaired adaptive cellular responses to oxidative stress and the pathogenesis of Alzheimer’s disease. Antioxid Redox Signal 14:1519–1534.  https://doi.org/10.1089/ars.2010.3569 CrossRefPubMedPubMedCentralGoogle Scholar
  107. Tresguerres IF, Tamimi F, Eimar H et al (2014) Resveratrol as anti-aging therapy for age-related bone loss. Rejuvenation Res 17:439–445.  https://doi.org/10.1089/rej.2014.1551 CrossRefPubMedGoogle Scholar
  108. Vander Haar E, Lee SI, Bandhakavi S et al (2007) Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol 9:316–323.  https://doi.org/10.1038/ncb1547 CrossRefPubMedGoogle Scholar
  109. Vellai T, Takacs-Vellai K, Zhang Y et al (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426:620.  https://doi.org/10.1038/426620a CrossRefPubMedGoogle Scholar
  110. Wang B, Abraham N, Gao G, Yang Q (2016) Dysregulation of autophagy and mitochondrial function in Parkinson’s disease. Transl Neurodegener 5:19.  https://doi.org/10.1186/s40035-016-0065-1 CrossRefPubMedPubMedCentralGoogle Scholar
  111. Weidberg H, Shvets E, Elazar Z (2011) Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem 80:125–156.  https://doi.org/10.1146/annurev-biochem-052709-094552 CrossRefPubMedGoogle Scholar
  112. Yang Z, Klionsky DJ (2010) Eaten alive: a history of macroautophagy. Nat Cell Biol 12:814–822.  https://doi.org/10.1038/ncb0910-814 CrossRefPubMedPubMedCentralGoogle Scholar
  113. Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14:959–965.  https://doi.org/10.1038/nm.1851 CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Abhishek Kumar Singh
    • 1
  • Sandeep Singh
    • 1
  • Syed Ibrahim Rizvi
    • 1
  1. 1.Department of BiochemistryUniversity of AllahabadAllahabadIndia

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