title: Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice.
abstract: We investigated whether chronic melatonin administration influences mitochondrial oxidative stress and life span in mice. Diaphragmatic mitochondria from female senescent prone (SAMP8) and senescent resistant (SAMR1) mice at 5 and 10 months of age were studied. Mitochondrial oxidative stress was determined by measuring the levels of lipid peroxidation, glutathione and glutathione disulfide, and glutathione peroxidase and reductase activities. Mitochondrial function was assessed by measuring the activity of the respiratory chain complexes and the ATP content. The results suggest that the age-dependent mitochondrial oxidative damage in the diaphragm of SAMP8 mice was accompanied by a reduction in the electron transport chain complex activities and in ATP levels. Furthermore, melatonin administration between 1 and 10 months of age normalized the redox and the bioenergetic status of the mitochondria and increased the ATP levels. Melatonin also increased both half-life and longevity, mainly in SAMP8 group. These results suggest an age-related increase in mitochondria vulnerability to oxidation in SAM mice at 10 months of age that was counteracted by melatonin therapy. The effects of melatonin on mitochondrial physiology probably underline the ability of the indoleamine to increase maximal life span in these animals.
authors.affiliation: Instituto de Biotecnología, Departamento de Fisiología, Universidad de Granada, Facultad de Medicina, Granada, Spain.
authors.forename: María I
authors.initials: MI
authors.lastname: Rodríguez
authors.forename: Germaine
authors.initials: G
authors.lastname: Escames
authors.forename: Luis C
authors.initials: LC
authors.lastname: López
authors.forename: Ana
authors.initials: A
authors.lastname: López
authors.forename: José A
authors.initials: JA
authors.lastname: García
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortiz
authors.forename: Vanesa
authors.initials: V
authors.lastname: Sánchez
authors.forename: Marta
authors.initials: M
authors.lastname: Romeu
authors.forename: Darío
authors.initials: D
authors.lastname: Acuña-Castroviejo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000187:drug effects / Q000502:physiology; D019588:Aging, Premature / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004579:Electron Transport / Q000502:physiology; D005260:Female; D008136:Longevity / Q000187:drug effects*; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008817:Mice, Mutant Strains; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000255:Adenosine Triphosphate; D008550:Melatonin