P66 SCH and its role in mitochondrial in homeostasis throughout the aging process

M.E. ELGUERO, N. VILLALBA,Y. ALIPPE; H. PÉREZ, I. REBAGLIATI,; PODEROSO J.JOSÉ, CARRERAS M. CECILIA

Mar del Plata

Congreso; LXI REUNION CIENTIFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA (SAIC) y LXIV REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGIA (SAI) Y XLVIII REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGIA EXPERIMENTAL; 2016

LXI REUNION CIENTIFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACION CLINICA (SAIC) y LXIV REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGIA (SAI) Y XLVIII REUNION ANUAL DE LA SOCIEDAD ARGENTINA DE FARMACOLOGIA EXPERIMENTAL

According to the free radicals aging theory, this process is due to accumulated oxidative damage caused by ROS generated during mitochondrial respiration. p66shc is a longevity genetic determinant that regulates apoptosis and metabolism through ROS generation. Our objective is to assess p66shc function on mitochondrial metabolism and physiology during the aging process. To this aim, we explored oxidative metabolism in brain and liver mitochondria of 3-24-month-old WT and KO mice for p66shc (p66shc-/-). We observed that p66shc-/- mouse, with longer life expectancy, exhibits changes in mitochondrial function throughout aging, such as decreased activity in the respiratory chain complexes, a reduction in H2O2 production rate, elevated ATP levels and a higher NAD /NADH ratio. P66shc-/- mice have difficulty gaining weight, which is shown by a 25% body weight reduction. All these conditions trigger proliferation and delay apoptosis using mechanisms such as mitochondrial biogenesis and dynamics. WB and qPCR showed regulation of proteins expression related to the mitochondrial fusion/fission and biogenesis such as Drp1, Opa1, Mfn2 and PGC1a during aging in KO mice. We conclude that the metabolic rate reduction in p66shc mice improves mitochondrial homeostasis coordinating mitochondrial biogenesis and the fusion/fission balance. This corresponds with a delay in the aging process.