title: Aging and vascular dysfunction: beneficial melatonin effects.
abstract: Aging is characterized by a progressive deterioration of physiological functions and metabolic processes. In aging and in diseases associated with the elderly, the loss of cells in vital structures or organs may be related to several factors. Sirtuin1 (SIRT1) is a member of the sirtuin family of protein deacetylases involved in life span extension; however, its involvement in the aging is not yet completely defined. Recently, melatonin, a pleiotropic molecule, shown to activate SIRT1 in primary neurons of young animals, as well as in aged neurons of a murine model of senescence. Melatonin is known to modulate oxidative stress-induced senescence and pro-survival pathways. We treated 6- and 15-week-old apolipoprotein E (APOE)-deficient mice (APOE 6w and 15w) with two melatonin formulations (FAST and RETARD) to evaluate their anti-aging effect. Morphological changes in vessels (aortic arch) of APOE mice were evaluated SIRT1, p53, endothelial nitric oxide synthase (eNOS), and endothelin-1 (ET-1) markers. We demonstrate that SIRT1 and eNOS decresed in APOE mice between 6 and 15 weeks and that aging induced an elevated expression of p53 and ET-1 in APOE animals. Melatonin improved the impairment of endothelial damage and reduced loss of SIRT1 and eNOS decreasing p53 and ET-1 expression. The RETARD melatonin preparation caused a greater improvement of vessel cytoarchitecture. In summary, we indicate that SIRT1-p53-eNOS axis as one of the important marker of advanced vascular dysfunctions linked to aging. Finally, we suggest that extended-release melatonin (RETARD) provides a more appropriate option for contrasting these dysfunctions compared with rapid release melatonin (FAST) administration.
authors: Department of Biomedical Sciences and Biotechnologies, Section of Human Anatomy, University of Brescia, Viale Europa 11, Brescia, Italy.
authors: Luigi Fabrizio
authors: LF
authors: Rodella
authors: Gaia
authors: G
authors: Favero
authors: Claudia
authors: C
authors: Rossini
authors: Eleonora
authors: E
authors: Foglio
authors: Francesca
authors: F
authors: Bonomini
authors: Russel J
authors: RJ
authors: Reiter
authors: Rita
authors: R
authors: Rezzani
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011863:Radioimmunoassay; D015854:Up-Regulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D008550:Melatonin