De Cavanagh 2008 Exp Gerontol
|de Cavanagh EM, Flores I, Ferder M, Inserra F, Ferder L (2008) Renin-angiotensin system inhibitors protect against age-related changes in rat liver mitochondrial DNA content and gene expression. Exp Gerontol 43:919-28.|
Abstract: Chronic renin-angiotensin system inhibition protects against liver fibrosis, ameliorates age-associated mitochondrial dysfunction and increases rodent lifespan. We hypothesized that life-long angiotensin-II-mediated stimulation of oxidant generation might participate in mitochondrial DNA "common deletion" formation, and the resulting impairment of bioenergetic capacity. Enalapril (10 mg/kg/d) or losartan (30 mg/kg/d) administered during 16.5 months were unable to prevent the age-dependent accumulation of rat liver mitochondrial DNA "common deletion", but attenuated the decrease of mitochondrial DNA content. This evidence - together with the enhancement of NRF-1 and PGC-1 mRNA contents - seems to explain why enalapril and losartan improved mitochondrial functioning and lowered oxidant production, since both the absolute number of mtDNA molecules and increased NRF-1 and PGC-1 transcription are positively related to mitochondrial respiratory capacity, and PGC-1 protects against increases in ROS production and damage. Oxidative stress evoked by abnormal respiratory function contributes to the pathophysiology of mitochondrial disease and human aging. If the present mitochondrial actions of renin-angiotensin system inhibitors are confirmed in humans they may modify the therapeutic significance of that strategy.
• Keywords: Aging, Mitochondria, DNA, Reactive oxygen species, Gene expression, Anti-aging, Antioxidant, PGC-1alpha
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, mtDNA;mt-genetics, Genetic knockout;overexpression Pathology: Aging;senescence Stress:Oxidative stress;RONS Organism: Rat Tissue;cell: Liver
Enzyme: Complex I Regulation: ADP Coupling state: OXPHOS