Sexual Dimorphism in Aging Mice: Effect of IGF-1 Gene Therapy on Motor and Cognitive Performance

FALOMIR LOCKHART, EUGENIA; BELLINI, MARIA JOSE; HERRERA, MACARENA LORENA; BASMADJIAN, OSVALDO MARTÍN; DOLCETTI, FRANCO JUAN CRUZ; HEREÑÚ, CLAUDIA BEATRIZ

Cordoba

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Previously, we reported some therapeutic benefits of IGF-1gene therapy administered in aging female rats. Here, weassessed the effects of gene therapy in the quantification offrailty through a clinical assessment of aging mice. The concept of frailty, which is a state of increased vulnerability toadverse health outcomes for people of the same age, wasdeveloped to explain the heterogeneity in clinical outcomesfor older patients, so in this study we compared the relationship between frailty index scores, treatment and sexes.We performed Clinical Frailty Index (! Susan E. Howlett,2013) and a set of behavioral tests in C57BL/6 mice of 74weeks. We divided the animals in three experimental groupsfor each sex and administered i.m. PBS, RAd-DS-Red, orRAd-IGF-1. After 21 days, we re-quantify FIs scores andmeasured locomotor activity, strength, and cognitive performance. We observed a reduction of FIs in both sexes in thegroup administered with IGF-1 compared with the PBSgroup. However, there were no significant differences inthe scores between sexes. Moreover, IGF-I gene therapyinduced a significant improvement in strength performancein males compared with PBS group and in females comparedwith RAd-DS-Red group. These preliminary results haveimportant implications in the design of therapeuticapproaches geared to identify basic mechanisms of cellulardysfunction in aging into meaningful treatment.