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Central control of spontaneous physical activity in mice submitted or not to caloric restriction during aging process

Grant number: 17/26075-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2018
Effective date (End): June 30, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Camila Aparecida Machado de Oliveira
Grantee:Izabelle Dias Benfato
Home Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Spontaneous Physical Activity (SPA) corresponds to activities of low intensity, such as walking, climbing stairs and activities of daily living. It is an important component of energy balance, and declines with aging. Currently, the central regulation of SPA is unknown. Caloric Restriction (CR) slows down the changes associated with aging and has a neuroprotective effect. In addition, the 30% CR seems to positively modulate the SPA. Thus, our goal is to verify whether the CR of 30% is able to prevent the decline of SPA during aging and identify which areas of the CNS are involved. C57bl /6 mice at 4 months of age will be divided into four groups: aged control (fed ad libitum up to 10 months of life); aged restricted (submitted to CR of 30% up to 10 months of life); young control (group fed ad libitum that will be euthanized at 4 months of age); young restricted (euthanized at 4 months of age after 1 month in CR of 30%). SPA and other locomotion parameters will be analyzed monthly. Metabolic and inflammatory parameters (glucose and insulin tolerance, triglyceride concentration, cholesterol, insulin, leptin, ghrelin, TNF-a and histological analysis of the liver) will be evaluated at the end of the study. We will also evaluate, by immunohistochemistry, markers of neuronal activity (delta fos), oxidative stress (8OHdG), and cell death (caspase 3) and survival (Bcl2) in encephalic areas related to locomotor activity, as well as orexin and BDNF expression, important neuromodulators of SPA. The hypothesis is that the CR of 30% is able to reduce the decline of SPA during aging and that this effect is related to higher neuronal activity and lower oxidative stress and cell death marking in the brain areas associated with positive regulation of SPA, including those expressing orexin and BDNF. (AU)