Protein malnutrition and premature aging: impact on cognitive skills and cellular senescence

NADINA M. FERRONI; EDUARDO T. CÁNEPA; SILVINA V. SONZOGNI

Córdoba

Congreso; XXXIV Anual Meeting of Argentine Society for Research in Neurosciences; 2019

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN NEUROCIENCIAS

Early‐life adversity, like protein malnutrition, increases the vulnerability to develop long-term effects on brain structures and function. The aim of this work is to study if perinatal protein malnutrition (PM) predisposes the occurrence of premature aging in a murine model and the mechanisms involved. Mice dams were fed with normal (NP, casein 20%) or low protein diet (LP, casein 8%) during gestation and lactation. Female offpring were evaluated at the ages of 2, 7 and 12 month. LP mice show a lower increase of weight along life and a tendency in having a lower mobility test at old age. We evaluated spatial memory and found that PM impairs this memory since they are young. Also, functionality of the olfactory system is lost earlier life in LP mice. We found a higher SA b-gal activity at old age in LP mice in the hippocampus that coincide with a premature upregulation of p21 senescence marker. We also found alterations in hippocampal neurogenesis at an old age showing LP mice a more immature dentate gyrus. Moreover, we evaluated oxidative stress and found a higher basal level in LP hippocampus together with a downregulation tendency of Catalase expression at a young age. We also found an upregulation by PM and age of Sirt7 which is recruited to DNA double-strand breaks. Together, our results show that perinatal PM causes long-term impairment in cognitive and physical skills through an accelerated senescence phenotype and increased in the oxidative stress in the hippocampus.