Skip to content
2000
image of Therapeutic Aspects of Melatonin-sirtuin Crosstalk: An Updated Review of Current Data Based on Cellular Mechanisms

Abstract

Melatonin, a master regulator of circadian rhythms and diverse physiological processes, exhibits complex interactions with various molecules. Sirtuins, a family of histone deacetylases, are key players in aging, stress responses, and metabolism and represent a critical target for melatonin. This review explores the multifaceted functions of melatonin and sirtuins, delving into the molecular mechanisms of their interaction. We further examine the impact of this synergy on various pathologies across different organs. Studies suggest that melatonin modulates SIRT1 and SIRT3 signaling pathways, offering protection in neurodegenerative, cardiovascular, skeletal, and pulmonary diseases, as well as renal and hepatic dysfunction. Additionally, melatonin-sirtuin interactions have been implicated in mitigating cancer development and promoting health in the female and male reproductive systems. Notably, the majority of studies across these systems demonstrate melatonin's ability to regulate SIRT1 and SIRT3 signaling, thereby alleviating associated pathologies. In conclusion, the intricate interplay between melatonin and, particularly, SIRT1 and SIRT3 emerges as a crucial modulator of diverse signaling pathways, with promising therapeutic implications for a wide range of diseases.

Loading

Article metrics loading...

/content/journals/cdt/10.2174/0113894501360934250512052503
2025-05-14
2025-09-14
Loading full text...

Full text loading...

References

  1. Oishi A. Gbahou F. Jockers R. Melatonin receptors, brain functions, and therapies. Handb. Clin. Neurol. 2021 179 345 356 10.1016/B978‑0‑12‑819975‑6.00022‑4 34225974
    [Google Scholar]
  2. Reiter R.J. Tan D.X. Fuentes-Broto L. Melatonin: A multitasking molecule. Prog. Brain Res. 2010 181 127 151 10.1016/S0079‑6123(08)81008‑4 20478436
    [Google Scholar]
  3. Finocchiaro L.M. Arzt E.S. Fernández-Castelo S. Criscuolo M. Finkielman S. Nahmod V. Serotonin and melatonin synthesis in peripheral blood mononuclear cells: Stimulation by interferon-gamma as part of an immunomodulatory pathway. J. Interferon Res. 1988 8 6 705 716 10.1089/jir.1988.8.705 3148005
    [Google Scholar]
  4. Quay W.B. Retinal and pineal hydroxyindole-o-methyl transferase activity in vertebrates. Life Sci. 1965 4 9 983 991 10.1016/0024‑3205(65)90202‑X 5840097
    [Google Scholar]
  5. Slominski A. Pisarchik A. Semak I. Sweatman T. Wortsman J. Szczesniewski A. Slugocki G. McNulty J. Kauser S. Tobin D.J. Jing C. Johansson O. Serotoninergic and melatoninergic systems are fully expressed in human skin. FASEB J. 2002 16 8 896 898 10.1096/fj.01‑0952fje 12039872
    [Google Scholar]
  6. Bonnefont-Rousselot D. Collin F. Melatonin: Action as antioxidant and potential applications in human disease and aging. Toxicology 2010 278 1 55 67 10.1016/j.tox.2010.04.008 20417677
    [Google Scholar]
  7. Carrascal L. Nunez-Abades P. Ayala A. Cano M. Role of melatonin in the inflammatory process and its therapeutic potential. Curr. Pharm. Des. 2018 24 14 1563 1588 10.2174/1381612824666180426112832 29701146
    [Google Scholar]
  8. 2019 Alzheimer’s disease facts and figures. Alzheimers Dement. 2019 15 3 321 387 10.1016/j.jalz.2019.01.010
    [Google Scholar]
  9. Mayo J.C. Sainz R.M. González Menéndez P. Cepas V. Tan D.X. Reiter R.J. Melatonin and sirtuins: A “not-so unexpected” relationship. J. Pineal Res. 2017 62 2 e12391 10.1111/jpi.12391 28109165
    [Google Scholar]
  10. Blander G. Guarente L. The Sir2 family of protein deacetylases. Annu. Rev. Biochem. 2004 73 1 417 435 10.1146/annurev.biochem.73.011303.073651 15189148
    [Google Scholar]
  11. Anderson R.M. Bitterman K.J. Wood J.G. Medvedik O. Sinclair D.A. Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 2003 423 6936 181 185 10.1038/nature01578 12736687
    [Google Scholar]
  12. Chalkiadaki A. Guarente L. High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction. Cell Metab. 2012 16 2 180 188 10.1016/j.cmet.2012.07.003 22883230
    [Google Scholar]
  13. Chang H.C. Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol. Metab. 2014 25 3 138 145 10.1016/j.tem.2013.12.001 24388149
    [Google Scholar]
  14. Cohen H.Y. Miller C. Bitterman K.J. Wall N.R. Hekking B. Kessler B. Howitz K.T. Gorospe M. de Cabo R. Sinclair D.A. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 2004 305 5682 390 392 10.1126/science.1099196 15205477
    [Google Scholar]
  15. Han D. Huang W. Li X. Gao L. Su T. Li X. Ma S. Liu T. Li C. Chen J. Gao E. Cao F. Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway. J. Pineal Res. 2016 60 2 178 192 10.1111/jpi.12299 26607398
    [Google Scholar]
  16. Zhao L. An R. Yang Y. Yang X. Liu H. Yue L. Li X. Lin Y. Reiter R.J. Qu Y. Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: The role of SIRT 1 signaling. J. Pineal Res. 2015 59 2 230 239 10.1111/jpi.12254 26094939
    [Google Scholar]
  17. Zhao L. Liu H. Yue L. Zhang J. Li X. Wang B. Lin Y. Qu Y. Melatonin Attenuates Early Brain Injury via the Melatonin Receptor/Sirt1/NF-κB Signaling Pathway Following Subarachnoid Hemorrhage in Mice. Mol. Neurobiol. 2017 54 3 1612 1621 10.1007/s12035‑016‑9776‑7 26867656
    [Google Scholar]
  18. Azedi F. Tavakol S. Ketabforoush A.H.M.E. Khazaei G. Bakhtazad A. Mousavizadeh K. Joghataei M.T. Modulation of autophagy by melatonin via sirtuins in stroke: From mechanisms to therapies. Life Sci. 2022 307 120870 10.1016/j.lfs.2022.120870 35948118
    [Google Scholar]
  19. Jung-Hynes B. Reiter R.J. Ahmad N. Sirtuins, melatonin and circadian rhythms: Building a bridge between aging and cancer. J. Pineal Res. 2010 48 1 9 19 10.1111/j.1600‑079X.2009.00729.x 20025641
    [Google Scholar]
  20. Reiter R.J. Tan D-X. Fuentes-Broto L. Chapter 8 - Melatonin: A Multitasking Molecule. Progress in Brain Research Martini L. Amsterdam, Netherlands Elsevier 2010 181 127 151 10.1016/S0079‑6123(08)81008‑4
    [Google Scholar]
  21. Dehdashtian E. Pourhanifeh M.H. Hemati K. Mehrzadi S. Hosseinzadeh A. Therapeutic application of nutraceuticals in diabetic nephropathy: Current evidence and future implications. Diabetes Metab. Res. Rev. 2020 36 8 e3336 10.1002/dmrr.3336 32415805
    [Google Scholar]
  22. Cardinali D.P. Larin F. Wurtman R.J. Action spectra for effects of light on hydroxyindole-o-methyl transferases in rat pineal, retina and harderian gland. Endocrinology 1972 91 4 877 886 10.1210/endo‑91‑4‑877 5051343
    [Google Scholar]
  23. Huether G. Poeggeler B. Reimer A. George A. Effect of tryptophan administration on circulating melatonin levels in chicks and rats: Evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. Life Sci. 1992 51 12 945 953 10.1016/0024‑3205(92)90402‑B 1518369
    [Google Scholar]
  24. Tan D. Manchester L.C. Reiter R.J. Qi W. Zhang M. Weintraub S.T. Cabrera J. Sainz R.M. Mayo J.C. Identification of highly elevated levels of melatonin in bone marrow: Its origin and significance. Biochim. Biophys. Acta, Gen. Subj. 1999 1472 1-2 206 214 10.1016/S0304‑4165(99)00125‑7 10572942
    [Google Scholar]
  25. Oblap R. Olszańska B. Presence and developmental regulation of serotonin N -acetyltransferase transcripts in oocytes and early quail embryos ( Coturnix coturnix japonica ). Mol. Reprod. Dev. 2003 65 2 132 140 10.1002/mrd.10236 12704723
    [Google Scholar]
  26. Coelho L.A. Peres R. Amaral F.G. Reiter R.J. Cipolla-Neto J. Daily differential expression of melatonin-related genes and clock genes in rat cumulus–oocyte complex: Changes after pinealectomy. J. Pineal Res. 2015 58 4 490 499 10.1111/jpi.12234 25807895
    [Google Scholar]
  27. Naranjo M.C. Guerrero J.M. Rubio A. Lardone P.J. Carrillo-Vico A. Carrascosa-Salmoral M.P. Jiménez-Jorge S. Arellano M.V. Leal-Noval S.R. Leal M. Lissen E. Molinero P. Melatonin biosynthesis in the thymus of humans and rats. Cell. Mol. Life Sci. 2007 64 6 781 790 10.1007/s00018‑007‑6435‑1 17334663
    [Google Scholar]
  28. Rosales-Corral S. Tan D.X. Reiter R.J. Valdivia-Velázquez M. Martínez-Barboza G. Pablo Acosta-Martínez J. Ortiz G.G. Orally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid- β peptide in rat brain: A comparative, in vivo study versus vitamin C and E. J. Pineal Res. 2003 35 2 80 84 10.1034/j.1600‑079X.2003.00057.x 12887649
    [Google Scholar]
  29. Pourhanifeh M.H. Hosseinzadeh A. Dehdashtian E. Hemati K. Mehrzadi S. Melatonin: New insights on its therapeutic properties in diabetic complications. Diabetol. Metab. Syndr. 2020 12 1 30 10.1186/s13098‑020‑00537‑z 32280378
    [Google Scholar]
  30. Wang J. Xiao X. Zhang Y. Shi D. Chen W. Fu L. Liu L. Xie F. Kang T. Huang W. Deng W. Simultaneous modulation of COX-2, p300, Akt, and Apaf-1 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells. J. Pineal Res. 2012 53 1 77 90 10.1111/j.1600‑079X.2012.00973.x 22335196
    [Google Scholar]
  31. Mehrzadi S. Pourhanifeh M.H. Mirzaei A. Moradian F. Hosseinzadeh A. An updated review of mechanistic potentials of melatonin against cancer: Pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress. Cancer Cell Int. 2021 21 1 188 10.1186/s12935‑021‑01892‑1 33789681
    [Google Scholar]
  32. Edlich F. BCL-2 proteins and apoptosis: Recent insights and unknowns. Biochem. Biophys. Res. Commun. 2018 500 1 26 34 10.1016/j.bbrc.2017.06.190 28676391
    [Google Scholar]
  33. Reiter R.J. Mayo J.C. Tan D.X. Sainz R.M. Alatorre-Jimenez M. Qin L. Melatonin as an antioxidant: Under promises but over delivers. J. Pineal Res. 2016 61 3 253 278 10.1111/jpi.12360 27500468
    [Google Scholar]
  34. Tan D.X. Manchester L.C. Terron M.P. Flores L.J. Reiter R.J. One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species? J. Pineal Res. 2007 42 1 28 42 10.1111/j.1600‑079X.2006.00407.x 17198536
    [Google Scholar]
  35. Ressmeyer A.R. Mayo J.C. Zelosko V. Sáinz R.M. Tan D.X. Poeggeler B. Antolín I. Zsizsik B.K. Reiter R.J. Hardeland R. Antioxidant properties of the melatonin metabolite N 1 -acetyl-5-methoxykynuramine (AMK): Scavenging of free radicals and prevention of protein destruction. Redox Rep. 2003 8 4 205 213 10.1179/135100003225002709 14599344
    [Google Scholar]
  36. Mayo J.C. Tan D.X. Sainz R.M. Lopez-Burillo S. Reiter R.J. Oxidative damage to catalase induced by peroxyl radicals: Functional protection by melatonin and other antioxidants. Free Radic. Res. 2003 37 5 543 553 10.1080/1071576031000083206 12797476
    [Google Scholar]
  37. Tan D. Reiter R. Manchester L. Yan M. El-Sawi M. Sainz R. Mayo J. Kohen R. Allegra M. Hardelan R. Chemical and physical properties and potential mechanisms: Melatonin as a broad spectrum antioxidant and free radical scavenger. Curr. Top. Med. Chem. 2002 2 2 181 197 10.2174/1568026023394443 11899100
    [Google Scholar]
  38. Mayo J.C. Sainz R.M. Antolín I. Herrera F. Martin V. Rodriguez C. Melatonin regulation of antioxidant enzyme gene expression. Cell. Mol. Life Sci. 2002 59 10 1706 1713 10.1007/PL00012498 12475181
    [Google Scholar]
  39. Galano A. Tan D.X. Reiter R.J. On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK. J. Pineal Res. 2013 54 3 245 257 10.1111/jpi.12010 22998574
    [Google Scholar]
  40. Mayo J.C. Sainz R.M. Tan D.X. Hardeland R. Leon J. Rodriguez C. Reiter R.J. Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J. Neuroimmunol. 2005 165 1-2 139 149 10.1016/j.jneuroim.2005.05.002 15975667
    [Google Scholar]
  41. Galano A. Medina M.E. Tan D.X. Reiter R.J. Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: A physicochemical analysis. J. Pineal Res. 2015 58 1 107 116 10.1111/jpi.12196 25424557
    [Google Scholar]
  42. Quintana C. Cabrera J. Perdomo J. Estévez F. Loro J.F. Reiter R.J. Quintana J. Melatonin enhances hyperthermia-induced apoptotic cell death in human leukemia cells. J. Pineal Res. 2016 61 3 381 395 10.1111/jpi.12356 27465521
    [Google Scholar]
  43. Reiter R.J. Tan D.X. Galano A. Melatonin: Exceeding expectations. Physiology (Bethesda) 2014 29 5 325 333 10.1152/physiol.00011.2014 25180262
    [Google Scholar]
  44. Korkmaz A. Sanchez-Barcelo E.J. Tan D.X. Reiter R.J. Role of melatonin in the epigenetic regulation of breast cancer. Breast Cancer Res. Treat. 2009 115 1 13 27 10.1007/s10549‑008‑0103‑5 18592373
    [Google Scholar]
  45. Venkatesh S. Workman J.L. Histone exchange, chromatin structure and the regulation of transcription. Nat. Rev. Mol. Cell Biol. 2015 16 3 178 189 10.1038/nrm3941 25650798
    [Google Scholar]
  46. Marmorstein R. Structure of histone deacetylases: Insights into substrate recognition and catalysis. Structure 2001 9 12 1127 1133 10.1016/S0969‑2126(01)00690‑6 11738039
    [Google Scholar]
  47. Kazantsev A.G. Thompson L.M. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat. Rev. Drug Discov. 2008 7 10 854 868 10.1038/nrd2681 18827828
    [Google Scholar]
  48. Loo S. Rine J. Silencers and domains of generalized repression. Science 1994 264 5166 1768 1771 10.1126/science.8209257 8209257
    [Google Scholar]
  49. Chalkiadaki A. Guarente L. The multifaceted functions of sirtuins in cancer. Nat. Rev. Cancer 2015 15 10 608 624 10.1038/nrc3985 26383140
    [Google Scholar]
  50. Nogueiras R. Habegger K.M. Chaudhary N. Finan B. Banks A.S. Dietrich M.O. Horvath T.L. Sinclair D.A. Pfluger P.T. Tschöp M.H. Sirtuin 1 and sirtuin 3: Physiological modulators of metabolism. Physiol. Rev. 2012 92 3 1479 1514 10.1152/physrev.00022.2011 22811431
    [Google Scholar]
  51. Lombard D.B. Alt F.W. Cheng H.L. Bunkenborg J. Streeper R.S. Mostoslavsky R. Kim J. Yancopoulos G. Valenzuela D. Murphy A. Yang Y. Chen Y. Hirschey M.D. Bronson R.T. Haigis M. Guarente L.P. Farese R.V. Jr Weissman S. Verdin E. Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol. 2007 27 24 8807 8814 10.1128/MCB.01636‑07 17923681
    [Google Scholar]
  52. Kitamura Y.I. Kitamura T. Kruse J.P. Raum J.C. Stein R. Gu W. Accili D. FoxO1 protects against pancreatic β cell failure through NeuroD and MafA induction. Cell Metab. 2005 2 3 153 163 10.1016/j.cmet.2005.08.004 16154098
    [Google Scholar]
  53. Cantó C. Gerhart-Hines Z. Feige J.N. Lagouge M. Noriega L. Milne J.C. Elliott P.J. Puigserver P. Auwerx J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009 458 7241 1056 1060 10.1038/nature07813 19262508
    [Google Scholar]
  54. Ford J. Jiang M. Milner J. Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival. Cancer Res. 2005 65 22 10457 10463 10.1158/0008‑5472.CAN‑05‑1923 16288037
    [Google Scholar]
  55. Rodgers J.T. Lerin C. Haas W. Gygi S.P. Spiegelman B.M. Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature 2005 434 7029 113 118 10.1038/nature03354 15744310
    [Google Scholar]
  56. Caton P.W. Nayuni N.K. Kieswich J. Khan N.Q. Yaqoob M.M. Corder R. Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5. J. Endocrinol. 2010 205 1 97 106 10.1677/JOE‑09‑0345 20093281
    [Google Scholar]
  57. Wang B. Hasan M.K. Alvarado E. Yuan H. Wu H. Chen W.Y. NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response. Oncogene 2011 30 8 907 921 10.1038/onc.2010.468 20956937
    [Google Scholar]
  58. Wang Y.C. Peterson S.E. Loring J.F. Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Res. 2014 24 2 143 160 10.1038/cr.2013.151 24217768
    [Google Scholar]
  59. Guo P. Pi H. Xu S. Zhang L. Li Y. Li M. Cao Z. Tian L. Xie J. Li R. He M. Lu Y. Liu C. Duan W. Yu Z. Zhou Z. Melatonin Improves mitochondrial function by promoting MT1/SIRT1/PGC-1 alpha-dependent mitochondrial biogenesis in cadmium-induced hepatotoxicity in vitro. Toxicol. Sci. 2014 142 1 182 195 10.1093/toxsci/kfu164 25159133
    [Google Scholar]
  60. Yang H. Yang T. Baur J.A. Perez E. Matsui T. Carmona J.J. Lamming D.W. Souza-Pinto N.C. Bohr V.A. Rosenzweig A. de Cabo R. Sauve A.A. Sinclair D.A. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 2007 130 6 1095 1107 10.1016/j.cell.2007.07.035 17889652
    [Google Scholar]
  61. Finley L.W.S. Carracedo A. Lee J. Souza A. Egia A. Zhang J. Teruya-Feldstein J. Moreira P.I. Cardoso S.M. Clish C.B. Pandolfi P.P. Haigis M.C. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization. Cancer Cell 2011 19 3 416 428 10.1016/j.ccr.2011.02.014 21397863
    [Google Scholar]
  62. Jeong S.M. Xiao C. Finley L.W.S. Lahusen T. Souza A.L. Pierce K. Li Y.H. Wang X. Laurent G. German N.J. Xu X. Li C. Wang R.H. Lee J. Csibi A. Cerione R. Blenis J. Clish C.B. Kimmelman A. Deng C.X. Haigis M.C. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 2013 23 4 450 463 10.1016/j.ccr.2013.02.024 23562301
    [Google Scholar]
  63. Sebastián C. Zwaans B.M.M. Silberman D.M. Gymrek M. Goren A. Zhong L. Ram O. Truelove J. Guimaraes A.R. Toiber D. Cosentino C. Greenson J.K. MacDonald A.I. McGlynn L. Maxwell F. Edwards J. Giacosa S. Guccione E. Weissleder R. Bernstein B.E. Regev A. Shiels P.G. Lombard D.B. Mostoslavsky R. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 2012 151 6 1185 1199 10.1016/j.cell.2012.10.047 23217706
    [Google Scholar]
  64. Lim J.H. Lee Y.M. Chun Y.S. Chen J. Kim J.E. Park J.W. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol. Cell 2010 38 6 864 878 10.1016/j.molcel.2010.05.023 20620956
    [Google Scholar]
  65. Bell E.L. Emerling B.M. Ricoult S.J.H. Guarente L. SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production. Oncogene 2011 30 26 2986 2996 10.1038/onc.2011.37 21358671
    [Google Scholar]
  66. Mukda S. Panmanee J. Boontem P. Govitrapong P. Melatonin administration reverses the alteration of amyloid precursor protein-cleaving secretases expression in aged mouse hippocampus. Neurosci. Lett. 2016 621 39 46 10.1016/j.neulet.2016.04.013 27068758
    [Google Scholar]
  67. Carloni S. Favrais G. Saliba E. Albertini M.C. Chalon S. Longini M. Gressens P. Buonocore G. Balduini W. Melatonin modulates neonatal brain inflammation through endoplasmic reticulum stress, autophagy, and mi R -34a/silent information regulator 1 pathway. J. Pineal Res. 2016 61 3 370 380 10.1111/jpi.12354 27441728
    [Google Scholar]
  68. Lee J.H. Moon J.H. Nazim U.M.D. Lee Y.J. Seol J.W. Eo S.K. Lee J.H. Park S.Y. Melatonin protects skin keratinocyte from hydrogen peroxide-mediated cell death via the SIRT1 pathway. Oncotarget 2016 7 11 12075 12088 10.18632/oncotarget.7679 26918354
    [Google Scholar]
  69. Carloni S. Albertini M.C. Galluzzi L. Buonocore G. Proietti F. Balduini W. Melatonin reduces endoplasmic reticulum stress and preserves sirtuin 1 expression in neuronal cells of newborn rats after hypoxia–ischemia. J. Pineal Res. 2014 57 2 192 199 10.1111/jpi.12156 24980917
    [Google Scholar]
  70. Bozaykut P. Sahin A. Karademir B. Ozer N.K. Endoplasmic reticulum stress related molecular mechanisms in nonalcoholic steatohepatitis. Mech. Ageing Dev. 2016 157 17 29 10.1016/j.mad.2016.07.001 27393639
    [Google Scholar]
  71. Zhou L. Chen X. Liu T. Gong Y. Chen S. Pan G. Cui W. Luo Z.P. Pei M. Yang H. He F. Melatonin reverses H 2 O 2 -induced premature senescence in mesenchymal stem cells via the SIRT 1-dependent pathway. J. Pineal Res. 2015 59 2 190 205 10.1111/jpi.12250 25975679
    [Google Scholar]
  72. Bai X.Z. He T. Gao J.X. Liu Y. Liu J.Q. Han S.C. Li Y. Shi J.H. Han J.T. Tao K. Xie S.T. Wang H.T. Hu D.H. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1. Sci. Rep. 2016 6 1 32199 10.1038/srep32199 27599451
    [Google Scholar]
  73. Shah S.A. Khan M. Jo M.H. Jo M.G. Amin F.U. Kim M.O. Melatonin stimulates the SIRT 1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain. CNS Neurosci. Ther. 2017 23 1 33 44 10.1111/cns.12588 27421686
    [Google Scholar]
  74. Yu L. Liang H. Dong X. Zhao G. Jin Z. Zhai M. Yang Y. Chen W. Liu J. Yi W. Yang J. Yi D. Duan W. Yu S. Reduced silent information regulator 1 signaling exacerbates myocardial ischemia–reperfusion injury in type 2 diabetic rats and the protective effect of melatonin. J. Pineal Res. 2015 59 3 376 390 10.1111/jpi.12269 26327197
    [Google Scholar]
  75. Yu L. Sun Y. Cheng L. Jin Z. Yang Y. Zhai M. Pei H. Wang X. Zhang H. Meng Q. Zhang Y. Yu S. Duan W. Melatonin receptor-mediated protection against myocardial ischemia/reperfusion injury: Role of SIRT 1. J. Pineal Res. 2014 57 2 228 238 10.1111/jpi.12161 25052362
    [Google Scholar]
  76. Dwaich K.H. Al-Amran F.G.Y. AL-Sheibani B.I.M. Al-Aubaidy H.A. Melatonin effects on myocardial ischemia–reperfusion injury: Impact on the outcome in patients undergoing coronary artery bypass grafting surgery. Int. J. Cardiol. 2016 221 977 986 10.1016/j.ijcard.2016.07.108 27441478
    [Google Scholar]
  77. Wei N. Pu Y. Yang Z. Pan Y. Liu L. RETRACTED: Therapeutic effects of melatonin on cerebral ischemia reperfusion injury: Role of Yap-OPA1 signaling pathway and mitochondrial fusion. Biomed. Pharmacother. 2019 110 203 212 10.1016/j.biopha.2018.11.060 30476721
    [Google Scholar]
  78. Yang X. Geng K.Y. Zhang Y.S. Zhang J.F. Yang K. Shao J.X. Xia W.L. Sirt3 deficiency impairs neurovascular recovery in ischemic stroke. CNS Neurosci. Ther. 2018 24 9 775 783 10.1111/cns.12853 29777578
    [Google Scholar]
  79. Verma R. Ritzel R.M. Crapser J. Friedler B.D. McCullough L.D. Evaluation of the neuroprotective effect of Sirt3 in experimental stroke. Transl. Stroke Res. 2019 10 1 57 66 10.1007/s12975‑017‑0603‑x 29302794
    [Google Scholar]
  80. Xiong Y. Wang M. Zhao J. Wang L. Li X. Zhang Z. Jia L. Han Y. SIRT3 is correlated with the malignancy of non-small cell lung cancer. Int. J. Oncol. 2017 50 3 903 910 10.3892/ijo.2017.3868 28197634
    [Google Scholar]
  81. Shioda N. Han F. Fukunaga K. Role of Akt and ERK signaling in the neurogenesis following brain ischemia. Int. Rev. Neurobiol. 2009 85 375 387 10.1016/S0074‑7742(09)85026‑5 19607982
    [Google Scholar]
  82. Shiojima I. Walsh K. Role of Akt signaling in vascular homeostasis and angiogenesis. Circ. Res. 2002 90 12 1243 1250 10.1161/01.RES.0000022200.71892.9F 12089061
    [Google Scholar]
  83. Hou X. Zeng H. He X. Chen J.X. Sirt3 is essential for apelin-induced angiogenesis in post-myocardial infarction of diabetes. J. Cell. Mol. Med. 2015 19 1 53 61 10.1111/jcmm.12453 25311234
    [Google Scholar]
  84. Yang X. Geng K. Zhang J. Zhang Y. Shao J. Xia W. Sirt3 mediates the inhibitory effect of adjudin on astrocyte activation and glial scar formation following ischemic stroke. Front. Pharmacol. 2017 8 943 10.3389/fphar.2017.00943 29311941
    [Google Scholar]
  85. Novgorodov S.A. Riley C.L. Keffler J.A. Yu J. Kindy M.S. Macklin W.B. Lombard D.B. Gudz T.I. SIRT3 deacetylates ceramide synthases: Implications for mitochondrial dysfunction and brain injury. J. Biol. Chem. 2016 291 4 1957 1973 10.1074/jbc.M115.668228 26620563
    [Google Scholar]
  86. Liu L. Chen H. Jin J. Tang Z. Yin P. Zhong D. Li G. Melatonin ameliorates cerebral ischemia/reperfusion injury through SIRT3 activation. Life Sci. 2019 239 117036 10.1016/j.lfs.2019.117036 31697951
    [Google Scholar]
  87. Carloni S. Perrone S. Buonocore G. Longini M. Proietti F. Balduini W. Melatonin protects from the long-term consequences of a neonatal hypoxic-ischemic brain injury in rats. J. Pineal Res. 2008 44 2 157 164 10.1111/j.1600‑079X.2007.00503.x 18289167
    [Google Scholar]
  88. Jiki Z. Lecour S. Nduhirabandi F. Cardiovascular benefits of dietary melatonin: A myth or a reality? Front. Physiol. 2018 9 528 10.3389/fphys.2018.00528 29867569
    [Google Scholar]
  89. Tobeiha M. Jafari A. Fadaei S. Mirazimi S.M.A. Dashti F. Amiri A. Khan H. Asemi Z. Reiter R.J. Hamblin M.R. Mirzaei H. Evidence for the benefits of melatonin in cardiovascular disease. Front. Cardiovasc. Med. 2022 9 888319 10.3389/fcvm.2022.888319 35795371
    [Google Scholar]
  90. Reiter R.J. Tan D.X. Paredes S.D. Fuentes-Broto L. Beneficial effects of melatonin in cardiovascular disease. Ann. Med. 2010 42 4 276 285 10.3109/07853890903485748 20455793
    [Google Scholar]
  91. Bindu S. Pillai V.B. Gupta M.P. Role of sirtuins in regulating pathophysiology of the heart. Trends Endocrinol. Metab. 2016 27 8 563 573 10.1016/j.tem.2016.04.015 27210897
    [Google Scholar]
  92. Vikram A. Lewarchik C.M. Yoon J.Y. Naqvi A. Kumar S. Morgan G.M. Jacobs J.S. Li Q. Kim Y.R. Kassan M. Liu J. Gabani M. Kumar A. Mehdi H. Zhu X. Guan X. Kutschke W. Zhang X. Boudreau R.L. Dai S. Matasic D.S. Jung S.B. Margulies K.B. Kumar V. Bachschmid M.M. London B. Irani K. Sirtuin 1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel. Nat. Med. 2017 23 3 361 367 10.1038/nm.4284 28191886
    [Google Scholar]
  93. Colak Y. Ozturk O. Senates E. Tuncer I. Yorulmaz E. Adali G. Doganay L. Enc F.Y. SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease. Med. Sci. Monit. 2011 17 5 HY5 HY9 10.12659/MSM.881749 21525818
    [Google Scholar]
  94. Lavu S. Boss O. Elliott P.J. Lambert P.D. Sirtuins — novel therapeutic targets to treat age-associated diseases. Nat. Rev. Drug Discov. 2008 7 10 841 853 10.1038/nrd2665 18827827
    [Google Scholar]
  95. Sheibani M. Azizi Y. Shayan M. Nezamoleslami S. Eslami F. Farjoo M.H. Dehpour A.R. Doxorubicin-induced cardiotoxicity: An overview on pre-clinical therapeutic approaches. Cardiovasc. Toxicol. 2022 22 4 292 310 10.1007/s12012‑022‑09721‑1 35061218
    [Google Scholar]
  96. Asher G. Gatfield D. Stratmann M. Reinke H. Dibner C. Kreppel F. Mostoslavsky R. Alt F.W. Schibler U. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 2008 134 2 317 328 10.1016/j.cell.2008.06.050 18662546
    [Google Scholar]
  97. Nakahata Y. Kaluzova M. Grimaldi B. Sahar S. Hirayama J. Chen D. Guarente L.P. Sassone-Corsi P. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 2008 134 2 329 340 10.1016/j.cell.2008.07.002 18662547
    [Google Scholar]
  98. Agil A. Navarro-Alarcón M. Ruiz R. Abuhamadah S. El-Mir M.Y. Vázquez G.F. Beneficial effects of melatonin on obesity and lipid profile in young Zucker diabetic fatty rats. J. Pineal Res. 2011 50 2 207 212 10.1111/j.1600‑079X.2010.00830.x 21087312
    [Google Scholar]
  99. Egan Benova T. Viczenczova C. Szeiffova Bacova B. Knezl V. Dosenko V. Rauchova H. Zeman M. Reiter R.J. Tribulova N. Obesity-associated alterations in cardiac connexin-43 and PKC signaling are attenuated by melatonin and omega-3 fatty acids in female rats. Mol. Cell. Biochem. 2019 454 1-2 191 202 10.1007/s11010‑018‑3463‑0 30446908
    [Google Scholar]
  100. Favero G. Stacchiotti A. Castrezzati S. Bonomini F. Albanese M. Rezzani R. Rodella L.F. Melatonin reduces obesity and restores adipokine patterns and metabolism in obese (ob/ob) mice. Nutr. Res. 2015 35 10 891 900 10.1016/j.nutres.2015.07.001 26250620
    [Google Scholar]
  101. Favero G. Franco C. Stacchiotti A. Rodella L.F. Rezzani R. RETRACTED: Sirtuin1 role in the melatonin protective effects against obesity-related heart injury. Front. Physiol. 2020 11 103 10.3389/fphys.2020.00103 32218740
    [Google Scholar]
  102. Zhang C.L. Feng H. Li L. Wang J.Y. Wu D. Hao Y.T. Wang Z. Zhang Y. Wu L.L. Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC-1α pathway. Biochim. Biophys. Acta, Gen. Subj. 2017 1861 1 1 Pt A 3085 3094 10.1016/j.bbagen.2016.10.022 27793739
    [Google Scholar]
  103. Lin J. Handschin C. Spiegelman B.M. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 2005 1 6 361 370 10.1016/j.cmet.2005.05.004 16054085
    [Google Scholar]
  104. Yu L. Gong B. Duan W. Fan C. Zhang J. Li Z. Xue X. Xu Y. Meng D. Li B. Zhang M. Bin Zhang Jin Z. Yu S. Yang Y. Wang H. Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: Role of AMPK-PGC-1α-SIRT3 signaling. Sci. Rep. 2017 7 1 41337 10.1038/srep41337 28120943
    [Google Scholar]
  105. Dhalla N. Elmoselhi A.B. Hata T. Makino N. Status of myocardial antioxidants in ischemia–reperfusion injury. Cardiovasc. Res. 2000 47 3 446 456 10.1016/S0008‑6363(00)00078‑X 10963718
    [Google Scholar]
  106. Slezak J. Tribulova N. Pristacova J. Uhrik B. Thomas T. Khaper N. Kaul N. Singal P.K. Hydrogen peroxide changes in ischemic and reperfused heart. Cytochemistry and biochemical and X-ray microanalysis. Am. J. Pathol. 1995 147 3 772 781 7677188
    [Google Scholar]
  107. Lesnefsky E.J. Chen Q. Tandler B. Hoppel C.L. Mitochondrial dysfunction and myocardial ischemia-reperfusion: Implications for novel therapies. Annu. Rev. Pharmacol. Toxicol. 2017 57 1 535 565 10.1146/annurev‑pharmtox‑010715‑103335 27860548
    [Google Scholar]
  108. Picca A. Lezza A.M.S. Regulation of mitochondrial biogenesis through TFAM–mitochondrial DNA interactions. Mitochondrion 2015 25 67 75 10.1016/j.mito.2015.10.001 26437364
    [Google Scholar]
  109. Yang Y. Duan W. Li Y. Jin Z. Yan J. Yu S. Yi D. Novel role of silent information regulator 1 in myocardial ischemia. Circulation 2013 128 20 2232 2240 10.1161/CIRCULATIONAHA.113.002480 24218438
    [Google Scholar]
  110. Hsu C.P. Zhai P. Yamamoto T. Maejima Y. Matsushima S. Hariharan N. Shao D. Takagi H. Oka S. Sadoshima J. Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation 2010 122 21 2170 2182 10.1161/CIRCULATIONAHA.110.958033 21060073
    [Google Scholar]
  111. Merx M.W. Weber C. Sepsis and the Heart. Circulation 2007 116 7 793 802 10.1161/CIRCULATIONAHA.106.678359 17698745
    [Google Scholar]
  112. Maejima Y. Isobe M. Sadoshima J. Regulation of autophagy by Beclin 1 in the heart. J. Mol. Cell. Cardiol. 2016 95 19 25 10.1016/j.yjmcc.2015.10.032 26546165
    [Google Scholar]
  113. Sun Y. Yao X. Zhang Q.J. Zhu M. Liu Z.P. Ci B. Xie Y. Carlson D. Rothermel B.A. Sun Y. Levine B. Hill J.A. Wolf S.E. Minei J.P. Zang Q.S. Beclin-1-dependent autophagy protects the heart during sepsis. Circulation 2018 138 20 2247 2262 10.1161/CIRCULATIONAHA.117.032821 29853517
    [Google Scholar]
  114. Chen X. Pan Z. Fang Z. Lin W. Wu S. Yang F. Li Y. Fu H. Gao H. Li S. Omega-3 polyunsaturated fatty acid attenuates traumatic brain injury-induced neuronal apoptosis by inducing autophagy through the upregulation of SIRT1-mediated deacetylation of Beclin-1. J. Neuroinflammation 2018 15 1 310 10.1186/s12974‑018‑1345‑8 30409173
    [Google Scholar]
  115. Pi Q.Z. Wang X.W. Jian Z.L. Chen D. Zhang C. Wu Q.C. Melatonin alleviates cardiac dysfunction via increasing sirt1-mediated beclin-1 deacetylation and autophagy during sepsis. Inflammation 2021 44 3 1184 1193 10.1007/s10753‑021‑01413‑2 33452667
    [Google Scholar]
  116. Zhang W. He B. Wu Y. Qiao J. Peng Z. Melatonin protects against sepsis-induced cardiac dysfunction by regulating apoptosis and autophagy via activation of SIRT1 in mice. Life Sci. 2019 217 8 15 10.1016/j.lfs.2018.11.055 30500551
    [Google Scholar]
  117. Arabacı Tamer S. Altınoluk T. Emran M. Korkmaz S. Yüksel R.G. Baykal Z. Dur Z.S. Levent H.N. Ural M.A. Yüksel M. Çevik Ö. Ercan F. Yıldırım A. Yeğen B.Ç. Melatonin alleviates ovariectomy-induced cardiovascular inflammation in sedentary or exercised rats by upregulating SIRT1. Inflammation 2022 45 6 2202 2222 10.1007/s10753‑022‑01685‑2 35665875
    [Google Scholar]
  118. Dominguez-Rodriguez A. Abreu-Gonzalez P. Reiter R.J. Melatonin and cardiovascular disease: Myth or reality? Rev. Esp. Cardiol. (Engl. Ed.) 2012 65 3 215 218 10.1016/j.rec.2011.10.011 22245066
    [Google Scholar]
  119. Ozkalayci F. Kocabas U. Altun B.U. Pandi-Perumal S. Altun A. Relationship between melatonin and cardiovascular disease. Cureus 2021 13 1 e12935 33654615
    [Google Scholar]
  120. Luo Q. Cai Y. Zhao Q. Jiang Y. Tian L. Liu Y. Liu W.J. Renal protective effects of melatonin in animal models of diabetes mellitus-related kidney damage: A systematic review and meta-analysis. J. Diabetes Res. 2022 2022 1 12 10.1155/2022/3770417 35746917
    [Google Scholar]
  121. Rahman A. Hasan A.U. Kobori H. Melatonin in chronic kidney disease: A promising chronotherapy targeting the intrarenal renin–angiotensin system. Hypertens. Res. 2019 42 6 920 923 10.1038/s41440‑019‑0223‑9 30760889
    [Google Scholar]
  122. Hrenak J. Paulis L. Repova K. Aziriova S. Nagtegaal E. Reiter R. Simko F. Melatonin and renal protection: Novel perspectives from animal experiments and human studies (review). Curr. Pharm. Des. 2014 21 7 936 949 10.2174/1381612820666140929092929 25269563
    [Google Scholar]
  123. Russcher M. Koch B. Nagtegaal E. van der Putten K. ter Wee P. Gaillard C. The role of melatonin treatment in chronic kidney disease. Front. Biosci. 2012 17 7 2644 2656 10.2741/4075 22652802
    [Google Scholar]
  124. Theofilis P. Vordoni A. Kalaitzidis R.G. The role of melatonin in chronic kidney disease and its associated risk factors: A new tool in our arsenal? Am. J. Nephrol. 2022 53 7 565 574 10.1159/000525441 35767942
    [Google Scholar]
  125. Owczarek A. Gieczewska K.B. Polanska M. Paterczyk B. Gruza A. Winiarska K. Melatonin lowers HIF-1α content in human proximal tubular cells (HK-2) due to preventing its deacetylation by sirtuin 1. Front. Physiol. 2021 11 572911 10.3389/fphys.2020.572911 33519498
    [Google Scholar]
  126. Nishiyama K. Hirai K. The melatonin agonist ramelteon induces duration-dependent clock gene expression through cAMP signaling in pancreatic INS-1 β-cells. PLoS One 2014 9 7 e102073 10.1371/journal.pone.0102073 25013953
    [Google Scholar]
  127. Zhang C. Suo M. Liu L. Qi Y. Zhang C. Xie L. Zheng X. Ma C. Li J. Yang J. Bu P. Melatonin alleviates contrast-induced acute kidney injury by activation of sirt3. Oxid. Med. Cell. Longev. 2021 2021 1 6668887 10.1155/2021/6668887 34122726
    [Google Scholar]
  128. Xiao Y.D. Huang Y.Y. Wang H.X. Wu Y. Leng Y. Liu M. Sun Q. Xia Z.Y. Thioredoxin-interacting protein mediates NLRP3 inflammasome activation involved in the susceptibility to ischemic acute kidney injury in diabetes. Oxid. Med. Cell. Longev. 2016 2016 1 2386068 10.1155/2016/2386068 27867451
    [Google Scholar]
  129. Zhang B. Zhai M. Li B. Liu Z. Li K. Jiang L. Zhang M. Yi W. Yang J. Yi D. Liang H. Jin Z. Duan W. Yu S. Honokiol ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by reducing oxidative stress and apoptosis through activating the SIRT1-Nrf2 signaling pathway. Oxid. Med. Cell. Longev. 2018 2018 1 3159801 10.1155/2018/3159801 29675132
    [Google Scholar]
  130. Shen X. Hu B. Xu G. Chen F. Ma R. Zhang N. Liu J. Ma X. Zhu J. Wu Y. Shen R. Activation of Nrf2/HO-1 pathway by glycogen synthase kinase-3β inhibition attenuates renal ischemia/reperfusion injury in diabetic rats. Kidney Blood Press. Res. 2017 42 2 369 378 10.1159/000477947 28624830
    [Google Scholar]
  131. Shi S. Lei S. Tang C. Wang K. Xia Z. Melatonin attenuates acute kidney ischemia/reperfusion injury in diabetic rats by activation of the SIRT1/Nrf2/HO-1 signaling pathway. Biosci. Rep. 2019 39 1 BSR20181614 10.1042/BSR20181614 30578379
    [Google Scholar]
  132. Palmieri T. Lavrentieva A. Greenhalgh D.G. Acute kidney injury in critically ill burn patients. Risk factors, progression and impact on mortality. Burns 2010 36 2 205 211 10.1016/j.burns.2009.08.012 19836141
    [Google Scholar]
  133. Steinvall I. Bak Z. Sjoberg F. Acute kidney injury is common, parallels organ dysfunction or failure, and carries appreciable mortality in patients with major burns: A prospective exploratory cohort study. Crit. Care 2008 12 5 R124 10.1186/cc7032 18847465
    [Google Scholar]
  134. Yeung F. Hoberg J.E. Ramsey C.S. Keller M.D. Jones D.R. Frye R.A. Mayo M.W. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004 23 12 2369 2380 10.1038/sj.emboj.7600244 15152190
    [Google Scholar]
  135. Cannino G. Ferruggia E. Luparello C. Rinaldi A.M. Cadmium and mitochondria. Mitochondrion 2009 9 6 377 384 10.1016/j.mito.2009.08.009 19706341
    [Google Scholar]
  136. Chou X. Ding F. Zhang X. Ding X. Gao H. Wu Q. Sirtuin-1 ameliorates cadmium-induced endoplasmic reticulum stress and pyroptosis through XBP-1s deacetylation in human renal tubular epithelial cells. Arch. Toxicol. 2019 93 4 965 986 10.1007/s00204‑019‑02415‑8 30796460
    [Google Scholar]
  137. Ge J. Zhang C. Sun Y.C. Zhang Q. Lv M.W. Guo K. Li J.L. Cadmium exposure triggers mitochondrial dysfunction and oxidative stress in chicken (Gallus gallus) kidney via mitochondrial UPR inhibition and Nrf2-mediated antioxidant defense activation. Sci. Total Environ. 2019 689 1160 1171 10.1016/j.scitotenv.2019.06.405 31466156
    [Google Scholar]
  138. Dong W. Yan L. Tan Y. Chen S. Zhang K. Gong Z. Liu W. Zou H. Song R. Zhu J. Liu G. Liu Z. Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1–PGC-1α pathway activation. Ecotoxicol. Environ. Saf. 2022 242 113879 10.1016/j.ecoenv.2022.113879 35841654
    [Google Scholar]
  139. Hong Y.A. Kim J.E. Jo M. Ko G.J. The role of sirtuins in kidney diseases. Int. J. Mol. Sci. 2020 21 18 6686 10.3390/ijms21186686 32932720
    [Google Scholar]
  140. Bian C. Ren H. Sirtuin family and diabetic kidney disease. Front. Endocrinol. (Lausanne) 2022 13 901066 10.3389/fendo.2022.901066 35774140
    [Google Scholar]
  141. Acuña Castroviejo D. López L.C. Escames G. López A. García J.A. Reiter R.J. Melatonin-mitochondria interplay in health and disease. Curr. Top. Med. Chem. 2011 11 2 221 240 10.2174/156802611794863517 21244359
    [Google Scholar]
  142. Dragicevic N. Copes N. O’Neal-Moffitt G. Jin J. Buzzeo R. Mamcarz M. Tan J. Cao C. Olcese J.M. Arendash G.W. Bradshaw P.C. Melatonin treatment restores mitochondrial function in Alzheimer’s mice: A mitochondrial protective role of melatonin membrane receptor signaling. J. Pineal Res. 2011 51 1 75 86 10.1111/j.1600‑079X.2011.00864.x 21355879
    [Google Scholar]
  143. El-Sokkary G.H. Nafady A.A. Shabash E.H. Melatonin administration ameliorates cadmium-induced oxidative stress and morphological changes in the liver of rat. Ecotoxicol. Environ. Saf. 2010 73 3 456 463 10.1016/j.ecoenv.2009.09.014 19913298
    [Google Scholar]
  144. Lagouge M. Argmann C. Gerhart-Hines Z. Meziane H. Lerin C. Daussin F. Messadeq N. Milne J. Lambert P. Elliott P. Geny B. Laakso M. Puigserver P. Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006 127 6 1109 1122 10.1016/j.cell.2006.11.013 17112576
    [Google Scholar]
  145. Rodgers J.T. Lerin C. Gerhart-Hines Z. Puigserver P. Metabolic adaptations through the PGC-1α and SIRT1 pathways. FEBS Lett. 2008 582 1 46 53 10.1016/j.febslet.2007.11.034 18036349
    [Google Scholar]
  146. Wang R. Li J.J. Diao S. Kwak Y.D. Liu L. Zhi L. Büeler H. Bhat N.R. Williams R.W. Park E.A. Liao F.F. Metabolic stress modulates Alzheimer’s β-secretase gene transcription via SIRT1-PPARγ-PGC-1 in neurons. Cell Metab. 2013 17 5 685 694 10.1016/j.cmet.2013.03.016 23663737
    [Google Scholar]
  147. Zhu H. Wang Z. Zhu X. Wu X. Li E. Xu Y. Icariin protects against brain injury by enhancing SIRT1-dependent PGC-1α Expression in experimental stroke. Neuropharmacology 2010 59 1-2 70 76 10.1016/j.neuropharm.2010.03.017 20381504
    [Google Scholar]
  148. Ren J. Jin M. You Z. Luo M. Han Y. Li G. Liu H. Melatonin prevents chronic intermittent hypoxia-induced injury by inducing sirtuin 1-mediated autophagy in steatotic liver of mice. Sleep Breath. 2019 23 3 825 836 10.1007/s11325‑018‑1741‑4 30411173
    [Google Scholar]
  149. Gerhardsson L. Englyst V. Lundström N.G. Sandberg S. Nordberg G. Cadmium, copper and zinc in tissues of deceased copper smelter workers. J. Trace Elem. Med. Biol. 2002 16 4 261 266 10.1016/S0946‑672X(02)80055‑4 12530590
    [Google Scholar]
  150. Chwełatiuk E. Włostowski T. Krasowska A. Bonda E. The effect of orally administered melatonin on tissue accumulation and toxicity of cadmium in mice. J. Trace Elem. Med. Biol. 2006 19 4 259 265 10.1016/j.jtemb.2005.10.006 16443174
    [Google Scholar]
  151. Wobser H. Dorn C. Weiss T.S. Amann T. Bollheimer C. Büttner R. Schölmerich J. Hellerbrand C. Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells. Cell Res. 2009 19 8 996 1005 10.1038/cr.2009.73 19546889
    [Google Scholar]
  152. Ahishali E. Demir K. Ahishali B. Akyuz F. Pinarbasi B. Poturoglu S. Ibrisim D. Gulluoglu M. Ozdil S. Besisik F. Kaymakoglu S. Boztas G. Cakaloglu Y. Mungan Z. Canberk Y. Okten A. Electron microscopic findings in non-alcoholic fatty liver disease: Is there a difference between hepatosteatosis and steatohepatitis? J. Gastroenterol. Hepatol. 2010 25 3 619 626 10.1111/j.1440‑1746.2009.06142.x 20370732
    [Google Scholar]
  153. Seki S. Kitada T. Yamada T. Sakaguchi H. Nakatani K. Wakasa K. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases. J. Hepatol. 2002 37 1 56 62 10.1016/S0168‑8278(02)00073‑9 12076862
    [Google Scholar]
  154. Puri N. Sodhi K. Haarstad M. Kim D.H. Bohinc S. Foglio E. Favero G. Abraham N.G. Heme induced oxidative stress attenuates sirtuin1 and enhances adipogenesis in mesenchymal stem cells and mouse pre-adipocytes. J. Cell. Biochem. 2012 113 6 1926 1935 10.1002/jcb.24061 22234917
    [Google Scholar]
  155. Yamazaki Y. Usui I. Kanatani Y. Matsuya Y. Tsuneyama K. Fujisaka S. Bukhari A. Suzuki H. Senda S. Imanishi S. Hirata K. Ishiki M. Hayashi R. Urakaze M. Nemoto H. Kobayashi M. Tobe K. Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice. Am. J. Physiol. Endocrinol. Metab. 2009 297 5 E1179 E1186 10.1152/ajpendo.90997.2008 19724016
    [Google Scholar]
  156. Ponugoti B. Kim D.H. Xiao Z. Smith Z. Miao J. Zang M. Wu S.Y. Chiang C.M. Veenstra T.D. Kemper J.K. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J. Biol. Chem. 2010 285 44 33959 33970 10.1074/jbc.M110.122978 20817729
    [Google Scholar]
  157. Bonomini F. Favero G. Rodella L.F. Moghadasian M.H. Rezzani R. Melatonin Modulation of Sirtuin-1 Attenuates Liver Injury in a Hypercholesterolemic Mouse Model. BioMed Res. Int. 2018 2018 1 9 10.1155/2018/7968452 29516009
    [Google Scholar]
  158. Li R. Xin T. Li D. Wang C. Zhu H. Zhou H. Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy. Redox Biol. 2018 18 229 243 10.1016/j.redox.2018.07.011 30056271
    [Google Scholar]
  159. Cardinali D.P. Ladizesky M.G. Boggio V. Cutrera R.A. Mautalen C. Melatonin effects on bone: Experimental facts and clinical perspectives. J. Pineal Res. 2003 34 2 81 87 10.1034/j.1600‑079X.2003.00028.x 12562498
    [Google Scholar]
  160. Munmun F. Witt-Enderby P.A. Melatonin effects on bone: Implications for use as a therapy for managing bone loss. J. Pineal Res. 2021 71 1 e12749 10.1111/jpi.12749 34085304
    [Google Scholar]
  161. Malakoti F. Zare F. Zarezadeh R. Raei Sadigh A. Sadeghpour A. Majidinia M. Yousefi B. Alemi F. The role of melatonin in bone regeneration: A review of involved signaling pathways. Biochimie 2022 202 56 70 10.1016/j.biochi.2022.08.008 36007758
    [Google Scholar]
  162. Kobayashi-Sun J. Suzuki N. Hattori A. Yamaguchi M. Kobayashi I. Melatonin suppresses both osteoblast and osteoclast differentiation through repression of epidermal Erk signaling in the zebrafish scale. Biochem. Biophys. Res. Commun. 2020 530 4 644 650 10.1016/j.bbrc.2020.07.075 32768192
    [Google Scholar]
  163. Zhang J. Xu Q. Sun W. Zhou X. Fu D. Mao L. New insights into the role of NLRP3 inflammasome in pathogenesis and treatment of chronic obstructive pulmonary disease. J. Inflamm. Res. 2021 14 4155 4168 10.2147/JIR.S324323 34471373
    [Google Scholar]
  164. Zheng S. Zhou C. Yang H. Li J. Feng Z. Liao L. Li Y. Melatonin accelerates osteoporotic bone defect repair by promoting osteogenesis–angiogenesis coupling. Front. Endocrinol. (Lausanne) 2022 13 826660 10.3389/fendo.2022.826660 35273570
    [Google Scholar]
  165. Yang C. Kang F. Huang X. Zhang W. Wang S. Han M. Zhang Z. Li J. Melatonin attenuates bone cancer pain via the SIRT1/HMGB1 pathway. Neuropharmacology 2022 220 109254 10.1016/j.neuropharm.2022.109254 36122662
    [Google Scholar]
  166. Zhou W. Liu Y. Shen J. Yu B. Bai J. Lin J. Guo X. Sun H. Chen Z. Yang H. Xu Y. Geng D. Melatonin increases bone mass around the prostheses of OVX rats by ameliorating mitochondrial oxidative stress via the SIRT3/SOD2 signaling pathway. Oxid. Med. Cell. Longev. 2019 2019 1 16 10.1155/2019/4019619 31110599
    [Google Scholar]
  167. Tresguerres I.F. Clemente C. Blanco L. Khraisat A. Tamimi F. Tresguerres J.A.F. Effects of local melatonin application on implant osseointegration. Clin. Implant Dent. Relat. Res. 2012 14 3 395 399 10.1111/j.1708‑8208.2010.00271.x 20455901
    [Google Scholar]
  168. Cutando A. Gómez-Moreno G. Arana C. Muñoz F. Lopez-Peña M. Stephenson J. Reiter R.J. Melatonin stimulates osteointegration of dental implants. J. Pineal Res. 2008 45 2 174 179 10.1111/j.1600‑079X.2008.00573.x 18298460
    [Google Scholar]
  169. Tan D-X. Melatonin: A potent, endogenous hydroxyl radical scavenger. Endocr. J. 1993 1 57 60
    [Google Scholar]
  170. Liu H.D. Ren M.X. Li Y. Zhang R.T. Ma N.F. Li T.L. Jiang W.K. Zhou Z. Yao X.W. Liu Z.Y. Yang M. Melatonin alleviates hydrogen peroxide induced oxidative damage in MC3T3-E1 cells and promotes osteogenesis by activating SIRT1. Free Radic. Res. 2022 56 1 63 76 10.1080/10715762.2022.2037580 35109721
    [Google Scholar]
  171. Ambrosi T.H. Scialdone A. Graja A. Gohlke S. Jank A.M. Bocian C. Woelk L. Fan H. Logan D.W. Schürmann A. Saraiva L.R. Schulz T.J. Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 2017 20 6 771 784.e6 10.1016/j.stem.2017.02.009 28330582
    [Google Scholar]
  172. Liu L.F. Shen W.J. Ueno M. Patel S. Kraemer F.B. Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes. BMC Genomics 2011 12 1 212 10.1186/1471‑2164‑12‑212 21545734
    [Google Scholar]
  173. Huang X. Chen W. Gu C. Liu H. Hou M. Qin W. Zhu X. Chen X. Liu T. Yang H. He F. Melatonin suppresses bone marrow adiposity in ovariectomized rats by rescuing the imbalance between osteogenesis and adipogenesis through SIRT1 activation. J. Orthop. Translat. 2023 38 84 97 10.1016/j.jot.2022.10.002 36381247
    [Google Scholar]
  174. Tseng P.C. Hou S.M. Chen R.J. Peng H.W. Hsieh C.F. Kuo M.L. Yen M.L. Resveratrol promotes osteogenesis of human mesenchymal stem cells by upregulating RUNX2 gene expression via the SIRT1/FOXO3A axis. J. Bone Miner. Res. 2011 26 10 2552 2563 10.1002/jbmr.460 21713995
    [Google Scholar]
  175. Bagherifard A. Hosseinzadeh A. Koosha F. Sheibani M. Karimi-Behnagh A. Reiter R.J. Mehrzadi S. Melatonin and bone-related diseases: An updated mechanistic overview of current evidence and future prospects. Osteoporos. Int. 2023 34 10 1677 1701 10.1007/s00198‑023‑06836‑1 37393580
    [Google Scholar]
  176. Yang C. Kang F. Huang X. Wu W. Hou G. Zheng K. Han M. Kan B. Zhang Z. Li J. Spinal sirtuin 2 attenuates bone cancer pain by deacetylating FoxO3a. Biochim. Biophys. Acta Mol. Basis Dis. 2024 1870 4 167129 10.1016/j.bbadis.2024.167129 38513990
    [Google Scholar]
  177. Habtemariam S. Daglia M. Sureda A. Selamoglu Z. Fuat Gulhan M. Mohammad Nabavi S. Melatonin and respiratory diseases: A review. Curr. Top. Med. Chem. 2016 17 4 467 488 10.2174/1568026616666160824120338 27558675
    [Google Scholar]
  178. Zhang L. Li F. Su X. Li Y. Wang Y. Fang R. Guo Y. Jin T. Shan H. Zhao X. Yang R. Shan H. Liang H. Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction. Exp. Mol. Med. 2019 51 7 1 12 10.1038/s12276‑019‑0273‑8 31273199
    [Google Scholar]
  179. Hosseinzadeh A. Pourhanifeh M.H. Amiri S. Sheibani M. Irilouzadian R. Reiter R.J. Mehrzadi S. Therapeutic potential of melatonin in targeting molecular pathways of organ fibrosis. Pharmacol. Rep. 2024 76 1 25 50 10.1007/s43440‑023‑00554‑5 37995089
    [Google Scholar]
  180. Hardeland R. Tan D.X. Protection by melatonin in respiratory diseases: Valuable information for the treatment of COVID-19. Melatonin Research 2020 3 3 264 275 10.32794/mr11250061
    [Google Scholar]
  181. He B. Zhang W. Qiao J. Peng Z. Chai X. Melatonin protects against COPD by attenuating apoptosis and endoplasmic reticulum stress via upregulating SIRT1 expression in rats. Can. J. Physiol. Pharmacol. 2019 97 5 386 391 10.1139/cjpp‑2018‑0529 30673309
    [Google Scholar]
  182. de Matos Cavalcante A.G. de Bruin P.F.C. de Bruin V.M.S. Nunes D.M. Pereira E.D.B. Cavalcante M.M. Andrade G.M. Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled study. J. Pineal Res. 2012 53 3 238 244 10.1111/j.1600‑079X.2012.00992.x 22507631
    [Google Scholar]
  183. Peng Z. Zhang W. Qiao J. He B. Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1β in rats with COPD. Int. Immunopharmacol. 2018 62 23 28 10.1016/j.intimp.2018.06.033 29990691
    [Google Scholar]
  184. Rajendrasozhan S. Yang S.R. Kinnula V.L. Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2008 177 8 861 870 10.1164/rccm.200708‑1269OC 18174544
    [Google Scholar]
  185. Yanagisawa S. Papaioannou A.I. Papaporfyriou A. Baker J.R. Vuppusetty C. Loukides S. Barnes P.J. Ito K. Decreased Serum Sirtuin-1 in COPD. Chest 2017 152 2 343 352 10.1016/j.chest.2017.05.004 28506610
    [Google Scholar]
  186. Shin N.R. Ko J.W. Kim J.C. Park G. Kim S.H. Kim M.S. Kim J.S. Shin I.S. Role of melatonin as an SIRT1 enhancer in chronic obstructive pulmonary disease induced by cigarette smoke. J. Cell. Mol. Med. 2020 24 1 1151 1156 10.1111/jcmm.14816 31762195
    [Google Scholar]
  187. Min T. Bodas M. Mazur S. Vij N. Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema. J. Mol. Med. (Berl.) 2011 89 6 577 593 10.1007/s00109‑011‑0732‑8 21318260
    [Google Scholar]
  188. Kelsen S.G. Duan X. Ji R. Perez O. Liu C. Merali S. Cigarette smoke induces an unfolded protein response in the human lung: A proteomic approach. Am. J. Respir. Cell Mol. Biol. 2008 38 5 541 550 10.1165/rcmb.2007‑0221OC 18079489
    [Google Scholar]
  189. Guo R. Liu W. Liu B. Zhang B. Li W. Xu Y. SIRT1 suppresses cardiomyocyte apoptosis in diabetic cardiomyopathy: An insight into endoplasmic reticulum stress response mechanism. Int. J. Cardiol. 2015 191 36 45 10.1016/j.ijcard.2015.04.245 25965594
    [Google Scholar]
  190. Han B. Li S. Lv Y. Yang D. Li J. Yang Q. Wu P. Lv Z. Zhang Z. Dietary melatonin attenuates chromium-induced lung injury via activating the Sirt1/Pgc-1α/Nrf2 pathway. Food Funct. 2019 10 9 5555 5565 10.1039/C9FO01152H 31429458
    [Google Scholar]
  191. Matthay M.A. McAuley D.F. Ware L.B. Clinical trials in acute respiratory distress syndrome: Challenges and opportunities. Lancet Respir. Med. 2017 5 6 524 534 10.1016/S2213‑2600(17)30188‑1 28664851
    [Google Scholar]
  192. Hummler E. Planès C. Importance of ENaC-mediated sodium transport in alveolar fluid clearance using genetically-engineered mice. Cell. Physiol. Biochem. 2010 25 1 063 070 10.1159/000272051 20054145
    [Google Scholar]
  193. Bourne R.S. Mills G.H. Melatonin: Possible implications for the postoperative and critically ill patient. Intensive Care Med. 2006 32 3 371 379 10.1007/s00134‑005‑0061‑x 16477412
    [Google Scholar]
  194. Li J. Liu L. Zhou X. Lu X. Liu X. Li G. Long J. Melatonin Attenuates Sepsis-Induced Acute Lung Injury Through Improvement of Epithelial Sodium Channel-Mediated Alveolar Fluid Clearance Via Activation of SIRT1/SGK1/Nedd4-2 Signaling Pathway. Front. Pharmacol. 2020 11 590652 10.3389/fphar.2020.590652 33362546
    [Google Scholar]
  195. Wulff P. Vallon V. Huang D.Y. Völkl H. Yu F. Richter K. Jansen M. Schlünz M. Klingel K. Loffing J. Kauselmann G. Bösl M.R. Lang F. Kuhl D. Impaired renal Na+ retention in the sgk1-knockout mouse. J. Clin. Invest. 2002 110 9 1263 1268 10.1172/JCI0215696 12417564
    [Google Scholar]
  196. Zhang X.Y. Li W. Zhang J.R. Li C.Y. Zhang J. Lv X.J. Roles of sirtuin family members in chronic obstructive pulmonary disease. Respir. Res. 2022 23 1 66 10.1186/s12931‑022‑01986‑y 35313881
    [Google Scholar]
  197. Jiang Y.Z. Huang X.R. Chang J. Zhou Y. Huang X.T. SIRT1: An intermediator of key pathways regulating pulmonary diseases. Lab. Invest. 2024 104 5 102044 10.1016/j.labinv.2024.102044 38452903
    [Google Scholar]
  198. Michan S. Sinclair D. Sirtuins in mammals: Insights into their biological function. Biochem. J. 2007 404 1 1 13 10.1042/BJ20070140 17447894
    [Google Scholar]
  199. Longo V.D. Kennedy B.K. Sirtuins in aging and age-related disease. Cell 2006 126 2 257 268 10.1016/j.cell.2006.07.002 16873059
    [Google Scholar]
  200. Lee C. Etchegaray J.P. Cagampang F.R.A. Loudon A.S.I. Reppert S.M. Posttranslational mechanisms regulate the mammalian circadian clock. Cell 2001 107 7 855 867 10.1016/S0092‑8674(01)00610‑9 11779462
    [Google Scholar]
  201. Blask D.E. Dauchy R.T. Sauer L.A. Putting cancer to sleep at night: The neuroendocrine/circadian melatonin signal. Endocr. J. 2005 27 2 179 188 10.1385/ENDO:27:2:179 16217131
    [Google Scholar]
  202. Lahti T.A. Partonen T. Kyyrönen P. Kauppinen T. Pukkala E. Night-time work predisposes to non-Hodgkin lymphoma. Int. J. Cancer 2008 123 9 2148 2151 10.1002/ijc.23566 18697199
    [Google Scholar]
  203. Viswanathan A.N. Schernhammer E.S. Circulating melatonin and the risk of breast and endometrial cancer in women. Cancer Lett. 2009 281 1 1 7 10.1016/j.canlet.2008.11.002 19070424
    [Google Scholar]
  204. Kubo T. Ozasa K. Mikami K. Wakai K. Fujino Y. Watanabe Y. Miki T. Nakao M. Hayashi K. Suzuki K. Mori M. Washio M. Sakauchi F. Ito Y. Yoshimura T. Tamakoshi A. Prospective cohort study of the risk of prostate cancer among rotating-shift workers: Findings from the Japan collaborative cohort study. Am. J. Epidemiol. 2006 164 6 549 555 10.1093/aje/kwj232 16829554
    [Google Scholar]
  205. Girgert R. Hanf V. Emons G. Gründker C. Membrane-bound melatonin receptor MT1 down-regulates estrogen responsive genes in breast cancer cells. J. Pineal Res. 2009 47 1 23 31 10.1111/j.1600‑079X.2009.00684.x 19522736
    [Google Scholar]
  206. Joo S.S. Yoo Y.M. Melatonin induces apoptotic death in LNCaP cells via p38 and JNK pathways: Therapeutic implications for prostate cancer. J. Pineal Res. 2009 47 1 8 14 10.1111/j.1600‑079X.2009.00682.x 19522739
    [Google Scholar]
  207. Erren T.C. Reiter R.J. Piekarski C. Light, timing of biological rhythms, and chronodisruption in man. Naturwissenschaften 2003 90 11 485 494 10.1007/s00114‑003‑0468‑6 14610644
    [Google Scholar]
  208. Jung-Hynes B. Ahmad N. Role of p53 in the anti-proliferative effects of Sirt1 inhibition in prostate cancer cells. Cell Cycle 2009 8 10 1478 1483 10.4161/cc.8.10.8408 19377286
    [Google Scholar]
  209. Jung-Hynes B. Ahmad N. SIRT1 controls circadian clock circuitry and promotes cell survival: A connection with age-related neoplasms. FASEB J. 2009 23 9 2803 2809 10.1096/fj.09‑129148 19439501
    [Google Scholar]
  210. Sun Y. Sun D. Li F. Tian L. Li C. Li L. Lin R. Wang S. Downregulation of Sirt1 by antisense oligonucleotides induces apoptosis and enhances radiation sensitization in A549 lung cancer cells. Lung Cancer 2007 58 1 21 29 10.1016/j.lungcan.2007.05.013 17624472
    [Google Scholar]
  211. Yuan J. Minter-Dykhouse K. Lou Z. A c-Myc–SIRT1 feedback loop regulates cell growth and transformation. J. Cell Biol. 2009 185 2 203 211 10.1083/jcb.200809167 19364925
    [Google Scholar]
  212. Firestein R. Blander G. Michan S. Oberdoerffer P. Ogino S. Campbell J. Bhimavarapu A. Luikenhuis S. de Cabo R. Fuchs C. Hahn W.C. Guarente L.P. Sinclair D.A. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS One 2008 3 4 e2020 10.1371/journal.pone.0002020 18414679
    [Google Scholar]
  213. Wang R.H. Zheng Y. Kim H.S. Xu X. Cao L. Lahusen T. Lee M.H. Xiao C. Vassilopoulos A. Chen W. Gardner K. Man Y.G. Hung M.C. Finkel T. Deng C.X. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol. Cell 2008 32 1 11 20 10.1016/j.molcel.2008.09.011 18851829
    [Google Scholar]
  214. Lai S.W. Liu Y.S. Lu D.Y. Tsai C.F. Melatonin modulates the microenvironment of glioblastoma multiforme by targeting sirtuin 1. Nutrients 2019 11 6 1343 10.3390/nu11061343 31207928
    [Google Scholar]
  215. Zheng B. Meng J. Zhu Y. Ding M. Zhang Y. Zhou J. Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS. J. Ovarian Res. 2021 14 1 152 10.1186/s13048‑021‑00912‑y 34758863
    [Google Scholar]
  216. Hampl R. Drábková P. Kanďár R. Stěpán J. Impact of oxidative stress on male infertility. Ceska Gynekol. 2012 77 3 241 245 22779727
    [Google Scholar]
  217. Rajender S. Mahdi A.A. Rajender S. Apoptosis spermatogenesis and male infertility. Front. Biosci. (Elite Ed.) 2012 E4 2 746 754 10.2741/e415 22201910
    [Google Scholar]
  218. Othman A.I. Edrees G.M. El-Missiry M.A. Ali D.A. Aboel-Nour M. Dabdoub B.R. Melatonin controlled apoptosis and protected the testes and sperm quality against bisphenol A-induced oxidative toxicity. Toxicol. Ind. Health 2016 32 9 1537 1549 10.1177/0748233714561286 25537623
    [Google Scholar]
  219. Xu G. Zhao J. Liu H. Wang J. Lu W. Melatonin inhibits apoptosis and oxidative stress of mouse leydig cells via a SIRT1-dependent mechanism. Molecules 2019 24 17 3084 10.3390/molecules24173084 31450679
    [Google Scholar]
  220. Zhang J. Fang Y. Tang D. Xu X. Zhu X. Wu S. Yu H. Cheng H. Luo T. Shen Q. Gao Y. Ma C. Liu Y. Wei Z. Chen X. Tao F. He X. Cao Y. Activation of MT1/MT2 to protect testes and leydig cells against cisplatin-induced oxidative stress through the SIRT1/Nrf2 signaling pathway. Cells 2022 11 10 1690 10.3390/cells11101690 35626727
    [Google Scholar]
  221. Wang P. Zhang S. Lin S. Lv Z. Melatonin ameliorates diabetic hyperglycaemia-induced impairment of Leydig cell steroidogenic function through activation of SIRT1 pathway. Reprod. Biol. Endocrinol. 2022 20 1 117 10.1186/s12958‑022‑00991‑6 35962432
    [Google Scholar]
  222. Rai S. Ghosh H. Modulation of human ovarian function by melatonin. Front. Biosci. (Elite Ed.) 2021 13 1 140 157 10.2741/875 33048779
    [Google Scholar]
  223. Tamura H. Jozaki M. Tanabe M. Shirafuta Y. Mihara Y. Shinagawa M. Tamura I. Maekawa R. Sato S. Taketani T. Takasaki A. Reiter R.J. Sugino N. Importance of melatonin in assisted reproductive technology and ovarian aging. Int. J. Mol. Sci. 2020 21 3 1135 10.3390/ijms21031135 32046301
    [Google Scholar]
  224. Ivanov D. Mazzoccoli G. Anderson G. Linkova N. Dyatlova A. Mironova E. Polyakova V. Kvetnoy I. Evsyukova I. Carbone A. Nasyrov R. Melatonin, its beneficial effects on embryogenesis from mitigating oxidative stress to regulating gene expression. Int. J. Mol. Sci. 2021 22 11 5885 10.3390/ijms22115885 34070944
    [Google Scholar]
  225. Tamura H. Kawamoto M. Sato S. Tamura I. Maekawa R. Taketani T. Aasada H. Takaki E. Nakai A. Reiter R.J. Sugino N. Long-term melatonin treatment delays ovarian aging. J. Pineal Res. 2017 62 2 e12381 10.1111/jpi.12381 27889913
    [Google Scholar]
  226. Huang Q. Chen S. Zhao Y. Chen J. Chen W. Lin S. Shi Q. Melatonin enhances autologous adipose-derived stem cells to improve mouse ovarian function in relation to the SIRT6/NF-κB pathway. Stem Cell Res. Ther. 2022 13 1 399 10.1186/s13287‑022‑03060‑2 35927704
    [Google Scholar]
  227. Ma M. Chen X.Y. Li B. Li X.T. Melatonin protects premature ovarian insufficiency induced by tripterygium glycosides: Role of SIRT1. Am. J. Transl. Res. 2017 9 4 1580 1602 28469767
    [Google Scholar]
  228. Lord T. Nixon B. Jones K.T. Aitken R.J. Melatonin prevents postovulatory oocyte aging in the mouse and extends the window for optimal fertilization in vitro. Biol. Reprod. 2013 88 3 67 10.1095/biolreprod.112.106450 23365415
    [Google Scholar]
  229. Shi J.M. Tian X.Z. Zhou G.B. Wang L. Gao C. Zhu S.E. Zeng S.M. Tian J.H. Liu G.S. Melatonin exists in porcine follicular fluid and improves in vitro maturation and parthenogenetic development of porcine oocytes. J. Pineal Res. 2009 47 4 318 323 10.1111/j.1600‑079X.2009.00717.x 19817971
    [Google Scholar]
  230. Tamura H. Takasaki A. Miwa I. Taniguchi K. Maekawa R. Asada H. Taketani T. Matsuoka A. Yamagata Y. Shimamura K. Morioka H. Ishikawa H. Reiter R.J. Sugino N. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J. Pineal Res. 2008 44 3 280 287 10.1111/j.1600‑079X.2007.00524.x 18339123
    [Google Scholar]
  231. Yang Q. Dai S. Luo X. Zhu J. Li F. Liu J. Yao G. Sun Y. Melatonin attenuates postovulatory oocyte dysfunction by regulating SIRT1 expression. Reproduction 2018 156 1 81 92 10.1530/REP‑18‑0211 29752296
    [Google Scholar]
  232. Tamura H. Nakamura Y. Korkmaz A. Manchester L.C. Tan D.X. Sugino N. Reiter R.J. Melatonin and the ovary: Physiological and pathophysiological implications. Fertil. Steril. 2009 92 1 328 343 10.1016/j.fertnstert.2008.05.016 18804205
    [Google Scholar]
  233. Reiter R.J. Guerrero J.M. Garcia J.J. Acuña-Castroviejo D. Reactive oxygen intermediates, molecular damage, and aging. Relation to melatonin. Ann. N. Y. Acad. Sci. 1998 854 1 410 424 10.1111/j.1749‑6632.1998.tb09920.x 9928448
    [Google Scholar]
  234. Reiter R.J. The ageing pineal gland and its physiological consequences. BioEssays 1992 14 3 169 175 10.1002/bies.950140307 1586370
    [Google Scholar]
  235. Volt H. García J.A. Doerrier C. Díaz-Casado M.E. Guerra-Librero A. López L.C. Escames G. Tresguerres J.A. Acuña-Castroviejo D. Same molecule but different expression: Aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin. J. Pineal Res. 2016 60 2 193 205 10.1111/jpi.12303 26681113
    [Google Scholar]
  236. Reiter R.J. Action spectra, dose-response relationships, and temporal aspects of light’s effects on the pineal gland. Ann. N. Y. Acad. Sci. 1985 453 1 215 230 10.1111/j.1749‑6632.1985.tb11812.x 3907458
    [Google Scholar]
  237. Pang S.F. Tang P.L. Decreased serum and pineal concentrations of melatonin and N-acetylserotonin in aged male hamsters. Horm. Res. 1983 17 4 228 234 10.1159/000179702 6884985
    [Google Scholar]
  238. Tresguerres J.A.F. Kireev R. Tresguerres A.F. Borras C. Vara E. Ariznavarreta C. Molecular mechanisms involved in the hormonal prevention of aging in the rat. J. Steroid Biochem. Mol. Biol. 2008 108 3-5 318 326 10.1016/j.jsbmb.2007.09.010 18252241
    [Google Scholar]
  239. Kireev R.A. Vara E. Tresguerres J.A.F. Growth hormone and melatonin prevent age-related alteration in apoptosis processes in the dentate gyrus of male rats. Biogerontology 2013 14 4 431 442 10.1007/s10522‑013‑9443‑6 23852044
    [Google Scholar]
  240. Kireev R.A. Vara E. Viña J. Tresguerres J.A.F. Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats. Age (Omaha) 2014 36 5 9707 10.1007/s11357‑014‑9707‑3 25135305
    [Google Scholar]
  241. Paredes S.D. Rancan L. Kireev R. González A. Louzao P. González P. Rodríguez-Bobada C. García C. Vara E. Tresguerres J.A.F. Melatonin counteracts at a transcriptional level the inflammatory and apoptotic response secondary to ischemic brain injury induced by middle cerebral artery blockade in aging rats. Biores. Open Access 2015 4 1 407 416 10.1089/biores.2015.0032 26594596
    [Google Scholar]
  242. Akbulut K.G. Aktas S.H. Akbulut H. The role of melatonin, sirtuin2 and FoXO1 transcription factor in the aging process of colon in male rats. Biogerontology 2015 16 1 99 108 10.1007/s10522‑014‑9540‑1 25430724
    [Google Scholar]
  243. Hirschey M.D. Shimazu T. Goetzman E. Jing E. Schwer B. Lombard D.B. Grueter C.A. Harris C. Biddinger S. Ilkayeva O.R. Stevens R.D. Li Y. Saha A.K. Ruderman N.B. Bain J.R. Newgard C.B. Farese R.V. Jr Alt F.W. Kahn C.R. Verdin E. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 2010 464 7285 121 125 10.1038/nature08778 20203611
    [Google Scholar]
  244. Sundaresan N.R. Gupta M. Kim G. Rajamohan S.B. Isbatan A. Gupta M.P. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J. Clin. Invest. 2009 119 9 2758 2771 10.1172/JCI39162 19652361
    [Google Scholar]
  245. Kim H.S. Patel K. Muldoon-Jacobs K. Bisht K.S. Aykin-Burns N. Pennington J.D. van der Meer R. Nguyen P. Savage J. Owens K.M. Vassilopoulos A. Ozden O. Park S.H. Singh K.K. Abdulkadir S.A. Spitz D.R. Deng C.X. Gius D. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 2010 17 1 41 52 10.1016/j.ccr.2009.11.023 20129246
    [Google Scholar]
  246. Quirós I. Sáinz R.M. Hevia D. García-Suárez O. Astudillo A. Rivas M. Mayo J.C. Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells. Int. J. Cancer 2009 125 7 1497 1504 10.1002/ijc.24501 19507253
    [Google Scholar]
  247. Reiter R.J. Tan D.X. Rosales-Corral S. Galano A. Jou M.J. Acuna-Castroviejo D. Melatonin mitigates mitochondrial meltdown: Interactions with SIRT3. Int. J. Mol. Sci. 2018 19 8 2439 10.3390/ijms19082439 30126181
    [Google Scholar]
  248. Corpas R. Griñán-Ferré C. Palomera-Ávalos V. Porquet D. García de Frutos P. Franciscato Cozzolino S.M. Rodríguez-Farré E. Pallàs M. Sanfeliu C. Cardoso B.R. Melatonin induces mechanisms of brain resilience against neurodegeneration. J. Pineal Res. 2018 65 4 e12515 10.1111/jpi.12515 29907977
    [Google Scholar]
  249. Houtkooper R.H. Pirinen E. Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 2012 13 4 225 238 10.1038/nrm3293 22395773
    [Google Scholar]
  250. Ribeiro R.F.N. Pereira D. de Almeida L.P. Silva M.M.C. Cavadas C. SIRT1 activation and its circadian clock control: A promising approach against (frailty in) neurodegenerative disorders. Aging Clin. Exp. Res. 2022 34 12 2963 2976 10.1007/s40520‑022‑02257‑y 36306110
    [Google Scholar]
  251. Soni S.K. Basu P. Singaravel M. Sharma R. Pandi-Perumal S.R. Cardinali D.P. Reiter R.J. Sirtuins and the circadian clock interplay in cardioprotection: Focus on sirtuin 1. Cell. Mol. Life Sci. 2021 78 6 2503 2515 10.1007/s00018‑020‑03713‑6 33388853
    [Google Scholar]
  252. Zhao L. Cao J. Hu K. He X. Yun D. Tong T. Han L. Sirtuins and their biological relevance in aging and age-related diseases. Aging Dis. 2020 11 4 927 945 10.14336/AD.2019.0820 32765955
    [Google Scholar]
  253. Wen Z. Chen Z. Li S. Zhang Q. Wang Y. Li Q. Lei Q. Melatonin protects against spinal cord injury through sirt-1 modulation of oxidative stress and neuronal cell loss. J. Biomed. Nanotechnol. 2023 19 7 1286 1294 10.1166/jbn.2023.3625
    [Google Scholar]
  254. Ansari Dezfouli M. Zahmatkesh M. Farahmandfar M. Khodagholi F. Melatonin protective effect against amyloid β-induced neurotoxicity mediated by mitochondrial biogenesis; involvement of hippocampal Sirtuin-1 signaling pathway. Physiol. Behav. 2019 204 65 75 10.1016/j.physbeh.2019.02.016 30769106
    [Google Scholar]
  255. Liu L. Cao Q. Gao W. Li B. Xia Z. Zhao B. Melatonin protects against focal cerebral ischemia-reperfusion injury in diabetic mice by ameliorating mitochondrial impairments: Involvement of the Akt-SIRT3-SOD2 signaling pathway. Aging (Albany NY) 2021 13 12 16105 16123 10.18632/aging.203137 34118791
    [Google Scholar]
  256. Zhai M. Li B. Duan W. Jing L. Zhang B. Zhang M. Yu L. Liu Z. Yu B. Ren K. Gao E. Yang Y. Liang H. Jin Z. Yu S. Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT 3-dependent regulation of oxidative stress and apoptosis. J. Pineal Res. 2017 63 2 e12419 10.1111/jpi.12419 28500761
    [Google Scholar]
  257. Wang Y. Zhang S. Ma Y. Xiang A. Sun H. Song J. Yang W. Li X. Xu H. Melatonin protected against myocardial infarction injury in rats through a Sirt6-dependent antioxidant pathway. Adv. Clin. Exp. Med. 2022 31 3 277 284 10.17219/acem/112060 35077033
    [Google Scholar]
  258. Jafari-Azad A. Hosseini L. Rajabi M. Høilund-Carlsen P.F. Vafaee M.S. Feyzizadeh S. Badalzadeh R. Nicotinamide mononucleotide and melatonin counteract myocardial ischemia-reperfusion injury by activating SIRT3/FOXO1 and reducing apoptosis in aged male rats. Mol. Biol. Rep. 2021 48 4 3089 3096 10.1007/s11033‑021‑06351‑8 33866495
    [Google Scholar]
  259. Naaz S. Mishra S. Pal P.K. Chattopadhyay A. Das A.R. Bandyopadhyay D. Activation of SIRT1/PGC 1α/SIRT3 pathway by melatonin provides protection against mitochondrial dysfunction in isoproterenol induced myocardial injury. Heliyon 2020 6 10 e05159 10.1016/j.heliyon.2020.e05159 33088945
    [Google Scholar]
  260. Wang B. Li J. Bao M. Chen R. Li H. Lu B. Melatonin attenuates diabetic myocardial microvascular injury through activating the AMPK/SIRT1 signaling pathway. Oxid. Med. Cell. Longev. 2021 2021 8882130 10.1155/2021/8882130 34336116
    [Google Scholar]
  261. Chen J. Xia H. Zhang L. Zhang H. Wang D. Tao X. Protective effects of melatonin on sepsis-induced liver injury and dysregulation of gluconeogenesis in rats through activating SIRT1/STAT3 pathway. Biomed. Pharmacother. 2019 117 109150 10.1016/j.biopha.2019.109150 31234024
    [Google Scholar]
  262. Ren X. Xu K. Xu J. Mei Q. Melatonin attenuates monocrotaline-induced hepatic sinusoidal obstruction syndrome in rats via activation of Sirtuin-3. J. Biochem. Mol. Toxicol. 2023 37 9 e23422 10.1002/jbt.23422 37350538
    [Google Scholar]
  263. Pi H. Xu S. Reiter R.J. Guo P. Zhang L. Li Y. Li M. Cao Z. Tian L. Xie J. Zhang R. He M. Lu Y. Liu C. Duan W. Yu Z. Zhou Z. SIRT3-SOD2-mROS-dependent autophagy in cadmium-induced hepatotoxicity and salvage by melatonin. Autophagy 2015 11 7 1037 1051 10.1080/15548627.2015.1052208 26120888
    [Google Scholar]
  264. Yalcin B. Yay A.H. Tan F.C. Özdamar S. Yildiz O.G. Investigation of the anti-oxidative and anti-inflammatory effects of melatonin on experimental liver damage by radiation. Pathol. Res. Pract. 2023 246 154477 10.1016/j.prp.2023.154477 37148837
    [Google Scholar]
  265. Kobroob A. Kongkaew A. Wongmekiat O. Melatonin reduces aggravation of renal ischemia–reperfusion injury in obese rats by maintaining mitochondrial homeostasis and integrity through AMPK/PGC-1α/SIRT3/SOD2 activation. Curr. Issues Mol. Biol. 2023 45 10 8239 8254 10.3390/cimb45100520 37886963
    [Google Scholar]
  266. Deng Z. He M. Hu H. Zhang W. Zhang Y. Ge Y. Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation. Autophagy 2023 20 1 1 15 10.1080/15548627.2023.2252265 37651673
    [Google Scholar]
  267. Chen W. Chen X. Chen A.C. Shi Q. Pan G. Pei M. Yang H. Liu T. He F. Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties. Free Radic. Biol. Med. 2020 146 92 106 10.1016/j.freeradbiomed.2019.10.412 31669348
    [Google Scholar]
  268. Zhang Y. Zhu X. Wang G. Chen L. Yang H. He F. Lin J. Melatonin rescues the Ti particle-impaired osteogenic potential of bone marrow mesenchymal stem cells via the SIRT1/SOD2 signaling pathway. Calcif. Tissue Int. 2020 107 5 474 488 10.1007/s00223‑020‑00741‑z 32767062
    [Google Scholar]
  269. Chen W. Lv N. Liu H. Gu C. Zhou X. Qin W. Melatonin improves the resistance of oxidative stress-induced cellular senescence in osteoporotic bone marrow mesenchymal stem cells. Oxid. Med. Cell. Longev. 2022 2022 7420726 10.1155/2022/7420726 35087617
    [Google Scholar]
  270. Ning L. Rui X. Guorui L. Tinglv F. Donghang L. Chenzhen X. Xiaojing W. Qing G. A novel mechanism for the protection against acute lung injury by melatonin: Mitochondrial quality control of lung epithelial cells is preserved through SIRT3-dependent deacetylation of SOD2. Cell. Mol. Life Sci. 2022 79 12 610 10.1007/s00018‑022‑04628‑0 36449070
    [Google Scholar]
  271. Rodríguez-Santana C. López-Rodríguez A. Martinez-Ruiz L. Florido J. Cela O. Capitanio N. Ramírez-Casas Y. Acuña-Castroviejo D. Escames G. The relationship between clock genes, sirtuin 1, and mitochondrial activity in head and neck squamous cell cancer: Effects of melatonin treatment. Int. J. Mol. Sci. 2023 24 19 15030 10.3390/ijms241915030 37834478
    [Google Scholar]
  272. Moreno-SanJuan S. Puentes-Pardo J.D. Casado J. Escudero-Feliu J. Khaldy H. Arnedo J. Carazo Á. León J. Agomelatine, a melatonin-derived drug, as a new strategy for the treatment of colorectal cancer. Antioxidants 2023 12 4 926 10.3390/antiox12040926 37107301
    [Google Scholar]
  273. Bonomini F. Favero G. Petroni A. Paroni R. Rezzani R. Melatonin modulates the sirt1-related pathways via transdermal cryopass-laser administration in prostate tumor xenograft. Cancers (Basel) 2023 15 20 4908 10.3390/cancers15204908 37894275
    [Google Scholar]
  274. Rodríguez-Santana C. Florido J. Martínez-Ruiz L. López-Rodríguez A. Acuña-Castroviejo D. Escames G. Role of melatonin in cancer: Effect on clock genes. Int. J. Mol. Sci. 2023 24 3 1919 10.3390/ijms24031919 36768253
    [Google Scholar]
  275. Cheng Y. Cai L. Jiang P. Wang J. Gao C. Feng H. Wang C. Pan H. Yang Y. SIRT1 inhibition by melatonin exerts antitumor activity in human osteosarcoma cells. Eur. J. Pharmacol. 2013 715 1-3 219 229 10.1016/j.ejphar.2013.05.017 23726949
    [Google Scholar]
  276. Wang M. Zhu C. Zeng L. Cheng L. Ma L. Zhang M. Zhang Y. Melatonin regulates the cross-talk between autophagy and apoptosis by SIRT3 in testicular Leydig cells. Biochem. Biophys. Res. Commun. 2021 555 182 189 10.1016/j.bbrc.2021.03.138 33823364
    [Google Scholar]
  277. Xu D. Liu L. Zhao Y. Yang L. Cheng J. Hua R. Zhang Z. Li Q. Melatonin protects mouse testes from palmitic acid-induced lipotoxicity by attenuating oxidative stress and DNA damage in a SIRT1-dependent manner. J. Pineal Res. 2020 69 4 e12690 10.1111/jpi.12690 32761924
    [Google Scholar]
  278. Kumar J. Haldar C. Verma R. Melatonin ameliorates LPS-induced testicular nitro-oxidative stress (iNOS/TNFα) and inflammation (NF-kB/COX-2) via modulation of SIRT-1. Reprod. Sci. 2021 28 12 3417 3430 10.1007/s43032‑021‑00597‑0 33929710
    [Google Scholar]
  279. Li B. He X. Zhuang M. Niu B. Wu C. Mu H. Tang F. Cui Y. Liu W. Zhao B. Peng S. Li G. Hua J. Melatonin ameliorates busulfan-induced spermatogonial stem cell oxidative apoptosis in mouse testes. Antioxid. Redox Signal. 2018 28 5 385 400 10.1089/ars.2016.6792 28027652
    [Google Scholar]
/content/journals/cdt/10.2174/0113894501360934250512052503
Loading
/content/journals/cdt/10.2174/0113894501360934250512052503
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: sirtuins family ; neurodegeneration ; circadian rhythm ; SIRT1 ; signaling pathways ; cancer ; aging ; SIRT3 ; Melatonin
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test