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In mammals, melatonin is primarily synthesized in the pineal gland and participates in a variety of multifaceted intracellular signaling networks and has been shown to synchronize CRs. Endogenous melatonin synthesis and its release tend to decrease progressively with advancing age. Older individuals experience frequent CR disruption, which hastens the process of aging. A profound understanding of the relationship between CRs and aging has the potential to improve existing treatments and facilitate development of novel chronotherapies that target age-related disorders. This review article aims to examine the circadian regulatory mechanisms in which melatonin plays a key role in signaling. We describe the basic architecture of the molecular circadian clock and its functional decline with age in detail. Furthermore, we discuss the role of melatonin in regulation of the circadian pacemaker and redox homeostasis during aging. Moreover, we also discuss the protective effect of exogenous melatonin supplementation in age-dependent CR disruption, which sheds light on this pleiotropic molecule and how it can be used as an effective chronotherapeutic medicine.<\/jats:p>","DOI":"10.1089\/rej.2023.0047","type":"journal-article","created":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T09:52:17Z","timestamp":1697536337000},"page":"229-241","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":33,"title":["Crosstalk Between Aging, Circadian Rhythm, and Melatonin"],"prefix":"10.1177","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1436-9752","authenticated-orcid":false,"given":"Avnish Kumar","family":"Verma","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Allahabad, Allahabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Idreesh","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, College of Applied Health Sciences in Ar Rass, Qassim University, Ar Rass, Saudi Arabia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fauzia","family":"Ashfaq","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Department, Applied Medical Sciences College, Jazan University, Jazan, Saudi Arabia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Ibrahim","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Allahabad, Allahabad, India."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00109-w"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148282"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0026-z"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0179-2"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12189"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.006"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90328"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22922-6"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0451-11.2011"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.042"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1096\/fba.2021-00125"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108750"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.112076"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26557"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2021.113960"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20513-5"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)00205-1"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.21773"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1523629113"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.650154"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00965"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2015.80.027490"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/382810a0"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl207"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001567"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226339"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.07.017"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00899-y"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.07.002"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrs.2009.08.035"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2010.03.006"},{"issue":"12","key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.1523\/JNEUROSCI.18-12-04767.1998","article-title":"Aging alters the rhythmic expression of vasoactive intestinal polypeptide mRNA but not arginine vasopressin mRNA in the suprachiasmatic nuclei of female rats","volume":"18","author":"Krajnak K","year":"1998","unstructured":"Krajnak K, , Kashon ML, , Rosewell KL, et al. 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