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The indoleamine is secreted by the pineal gland during the night, following a circadian rhythm. The highest plasmatic levels are reached during the night, whereas the lowest levels are achieved during the day. In addition to the pineal gland, other organs and tissues also produce melatonin, like, for example, the retina, Harderian glands, gut, ovaries, testes, skin, leukocytes, or bone marrow. The list of organs is extensive, including the cerebellum, airway epithelium, liver, kidney, adrenals, thymus, thyroid, pancreas, carotid body, placenta, and endometrium. At all these locations, the availability of melatonin is intended for local use. Interestingly, a decline of the circadian amplitude of the melatonin secretion occurs in old subjects in comparison to that found in younger subjects. Moreover, genetic and environmental factors are the primary causes of diseases, and oxidative stress is a key contributor to most pathologies. Numerous studies exist that show interesting effects of melatonin in different models of disease. Impairment in its secretion might have deleterious consequences for cellular physiology. In this regard, melatonin is a natural compound that is a carrier of a not yet completely known potential that deserves consideration. Thus, melatonin has emerged as a helpful ally that could be considered as a guard with powerful tools to orchestrate homeostasis in the body, majorly based on its antioxidant effects. In this review, we provide an overview of the widespread actions of melatonin against diseases preferentially affecting the elderly.<\/jats:p>","DOI":"10.3390\/biom15050682","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:06:21Z","timestamp":1746677181000},"page":"682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Melatonin Interplay in Physiology and Disease\u2014The Fountain of Eternal Youth Revisited"],"prefix":"10.3390","volume":"15","author":[{"given":"C\u00e1ndido","family":"Ortiz-Plac\u00edn","sequence":"first","affiliation":[{"name":"Institute of Molecular Pathology Biomarkers, University of Extremadura, Avenida de las Ciencias s\/n, E-10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8687-2445","authenticated-orcid":false,"given":"Gin\u00e9s Mar\u00eda","family":"Salido","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology Biomarkers, University of Extremadura, Avenida de las Ciencias s\/n, E-10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8380-0270","authenticated-orcid":false,"given":"Antonio","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology Biomarkers, University of Extremadura, Avenida de las Ciencias s\/n, E-10003 Caceres, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101036","DOI":"10.1016\/j.arr.2020.101036","article-title":"Biomarkers, Oxidative Stress and Autophagy in Skin Aging","volume":"59","author":"Gu","year":"2020","journal-title":"Ageing Res. 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