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Melatonin as antioxidant, geroprotector and anticarcinogen
Vladimir N Anisimov1, Irina G Popovich, Mark A Zabezhinski
1Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 197758, Russia. aging@mail.ru
Biochimica Et Biophysica Acta
|May 9, 2006
Summary
Melatonin, a pineal hormone, extended the lifespan of mice and rats and inhibited various cancers in rodents. This study investigated melatonin's effects on longevity and carcinogenesis, revealing its antioxidant and gene-regulating properties.
Area of Science:
- Gerontology and Toxicology
- Molecular Biology and Genetics
- Cancer Research
Background:
- The pineal indole hormone melatonin is known to influence various physiological processes.
- Previous studies have suggested potential roles for melatonin in aging and cancer prevention.
- Understanding melatonin's molecular mechanisms is crucial for its therapeutic applications.
Purpose of the Study:
- To investigate the effects of melatonin on the lifespan of mice, rats, and fruit flies.
- To evaluate melatonin's efficacy in preventing various types of chemically induced carcinogenesis in rodents.
- To identify molecular targets and pathways regulated by melatonin using gene expression profiling.
Main Methods:
- Long-term administration of melatonin to mice, rats, and fruit flies (Drosophila melanogaster).
- Assessment of lifespan and survival rates in treated animal models.
- Evaluation of melatonin's genotoxicity using Ames test and COMET assay.
- Carcinogenesis inhibition studies using various chemical carcinogens in rodents.
- Gene expression profiling in mouse heart and brain tissues using cDNA arrays.
Main Results:
- Melatonin administration increased the mean lifespan in female mice and overall survival in rats.
- In fruit flies, melatonin increased longevity when added to food throughout their lifespan.
- Melatonin demonstrated potent antioxidant activity in vitro and in vivo.
- Melatonin inhibited spontaneous and chemically induced carcinogenesis in multiple rodent models.
- Gene expression analysis revealed melatonin regulates genes involved in cell cycle, defense, protein transport, mitochondrial function, and calcium exchange.
- Melatonin modulated the expression of several oncogenesis-related genes.
Conclusions:
- Melatonin effectively extends lifespan and enhances survival in several animal models.
- Melatonin possesses significant anti-carcinogenic properties against a wide range of induced cancers.
- Melatonin's molecular effects involve the regulation of key cellular processes, including cell cycle, defense mechanisms, and calcium signaling.
- Melatonin shows promise as a potential agent for preventing premature aging and carcinogenesis.