Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions
Open accessAbstract
Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters that aid in the rapid uptake of melatonin by these organelles against a gradient. Moreover, we predicted several years ago that, because of their origin from melatonin-producing bacteria, mitochondria likely also synthesize melatonin. Data accumulated within the last year supports this prediction. A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the “free radical theory of aging”, including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age.
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Supplemental melatonin may offset some of the decline accompanying the aging process through physiological regeneration, as documented in animal and human studies.
“There may be the ability to offset some of the decline accompanying the aging process through physiological regeneration with supplemental melatonin, as has been documented in animal and human studies [36].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [36]
Mitochondrial dysfunction is one of the mechanisms related to diseases of aging.
“Mitochondrial dysfunction is one of the mechanisms related to diseases of aging [36].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [36]
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Self-citationMelatonin Enters the Cerebrospinal Fluid through the Pineal Recess
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Self-citationOn the pH-dependent yield of hydroxyl radical products from peroxynitrite
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Physiological levels of melatonin contribute to the antioxidant capacity of human serum
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Self-citationThe Melatonin MT1 Receptor Axis Modulates Mutant Huntingtin-Mediated Toxicity
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Melatonin: A Clock‐Output, A Clock‐Input
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Self-citationEndocrine Aspects of the Mammalian Pineal Gland: A Review
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Self-citationMechanisms of Melatonin in Alleviating Alzheimer’s Disease
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Self-citationAugmentation of indices of oxidative damage in life-long melatonin-deficient rats
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Self-citationMelatonin: A pleiotropic molecule that modulates DNA damage response and repair pathways
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Self-citationMelatonin: Daily Cycle in Plasma and Cerebrospinal Fluid of Calves
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Self-citationMelatonin and female reproduction
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New Perspective for an Old Antidiabetic Drug: Metformin as Anticancer Agent
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Self-citationA new balancing act: The many roles of melatonin and serotonin in plant growth and development
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Self-citationMelatonin uptake through glucose transporters: a new target for melatonin inhibition of cancer
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Melatonin receptors: Current status, facts, and hypotheses
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Melatonin and the electron transport chain
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Melatonin and mitochondrial function during ischemia/reperfusion injury
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Melatonin combats molecular terrorism at the mitochondrial level
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Self-citationProtective role of melatonin in mitochondrial dysfunction and related disorders
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Melatonin attenuates postmyocardial infarction injury via increasing Tom70 expression
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Clinical Uses of Melatonin in Neurological Diseases and Mental and Behavioural Disorders
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MAO inhibitors and oxidant stress in aging brain tissue
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Self-citationMelatonin, mitochondria and hypertension
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Which is the most significant cause of aging?
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Melatonin enhances hyperthermia‐induced apoptotic cell death in human leukemia cells
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Self-citationDramatic Rises of Melatonin and 5-Methoxytryptamine in Gonyaulax Exposed to Decreased Temperature
Fuhrberg, B., Hardeland, R., Pöeggeler, B., et al. (1997) · Biological Rhythm Research · doi:10.1076/brhm.28.1.144.12978 · Cited by 46 · see citing works
Melatonin enhances survival and preserves functional integrity of stem cells: A review
Lee, M. S.-S., Yin, T., Sung, P., Chiang, J. Y., Sun, C., & Yip, H. (2016) · Journal of Pineal Research · doi:10.1111/jpi.12372 · Cited by 45 · see citing works
Melatonin’s role in preventing toxin-related and sepsis-mediated hepatic damage: A review
Zubero, E. E., Alatorre-Jiménez, M. A., López‐Pingarrón, L., Reyes-Gonzales, M. C., Souza, P. A., Cantín-Golet, A., Ruiz-Ruiz, F. J., Tan, D., García, J. J., & Reiter, R. J. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.01.018 · Cited by 43 · see citing works
Self-citationRedox regulation and pro-oxidant reactions in the physiology of circadian systems
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Sung, J., Cho, E., Kim, M. O., & Koh, P. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2008.00661.x · Cited by 41 · see citing works
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Mitochondria in skin health, aging, and disease
Sreedhar, A., Aguilera-Aguirre, L., & Singh, K. K. (2020) · Cell Death & Disease · doi:10.1038/s41419-020-2649-z · Cited by 339 · see citing works
Melatonin in type 2 diabetes mellitus and obesity
Karamitri, A., & Jockers, R. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0130-1 · Cited by 268 · see citing works
Is Melatonin the Cornucopia of the 21st Century?
Ferlazzo, N., Andolina, G., Cannata, A., Costanzo, M. G., Rizzo, V., Currò, M., Ientile, R., & Caccamo, D. (2020) · Antioxidants · doi:10.3390/antiox9111088 · Cited by 189 · see citing works
Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022) · Nutrients · doi:10.3390/nu14193934 · Cited by 176 · see citing works
“Mitochondrial dysfunction is one of the mechanisms related to diseases of aging [36].”
BackgroundResultInfluentialMitochondria: the birth place, battle ground and the site of melatonin metabolism in cells
Tan, D.-X., & Reiter, R. J. (2019) · Melatonin Research · doi:10.32794/mr11250011 · Cited by 172 · see citing works
“The major function of melatonin is to prevent mitochondrial damage caused by oxidative stress; this action has been extensively reviewed (87, 91).”
BackgroundSelf-citationAdvancements in therapeutic drugs targeting of senescence
Zhu, M., Meng, P., Ling, X., & Zhou, L. (2020) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622320964125 · Cited by 68 · see citing works
- Authors
- Reiter, R., Tan, D., Rosales-Corral, S., Galano, A., Zhou, X., & Xu, B.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Centro de Investigacion Biomedica de Occidente, Instituo Mexicana del Seguro Social, Guadalajara 44346, Mexico
- Universidad Autónoma Metropolitana (MX)
- Corresponding author
- Reiter, Russel
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2018-02-24
- Volume
- 23
- Issue
- 2
- Pages
- 509
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC6017324
- OpenAlex
- W2790776869
- Cited by
- 393
- References
- 221
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 40 · 2023: 87 · 2022: 54 · 2021: 58 · 2020: 52 · 2019: 25 · 2018: 25 · 2016: 1
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melatonin, mitochondria, oxidative stress, free radicals, antioxidant activity, anti-aging, free radical theory of aging, age-related diseases, mitochondrial membrane
- MeSH terms
- Aging, Animals, Antioxidants, Free Radicals, Humans, Melatonin, Mitochondria, Organ Specificity, Oxidation-Reduction, Oxidative Phosphorylation, Reactive Oxygen Species, Oxidative Stress
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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