IGF-1 gene therapy in aging mice: comparisons of frailty index between sexes

HERRERA ML; FALOMIR-LOCKHART E; DOLCETTI F J-C; BASMADJIAN OM; HEREÑÚ CB; BELLINI MJ

Berlín

Congreso; 11º FENS Forum of Neuroscience 2018; 2018

Federation of European Neuroscience Societies

We previously reported some therapeutical benefits of IGF-1 gene therapy administered intramuscularly in a brain injury model. Here we assessed the effects of gene therapy in the quantification of frailty through a clinical assessment of aging mice. The concept of frailty, which is a state of increased vulnerability to adverse health outcomes for people of the same age, was developed to explain the heterogeneity in clinical outcomes for older patients, so in this study we compared the relationship between frailty index scores, treatment and sexes. We performed 31-items Clinical Frailty Index (© Susan E. Howlett, 2013) and a set of behavioral tests in C57BL/6 mice of 24 months (pretreatment stage), then we divided the animals in three experimental groups for each sex and administered i.m. PBS, RAd-DS-Red or RAd-IGF-1. After 21 days, we re-quantify FIs scores (postreatment stage) and performed a wire mesh ramp test in order to assess strength. We observed a reduction of FIs in both sexes in the group administered with IGF-1 compared with the PBS group (p<0.05). However, there were no significant differences in the scores between sexes. Moreover, IGF-I gene therapy induced a significant improvement in strength performance in males compared with PBS group (p<0.05) and in females compared with RAd-DS-Red group (p<0.05). These therapuetical effects observed in aged mice could be the result of additive effects of exogenous IGF-1 acting at multiple CNS regions, which encourage us to deepen the studies under this experimental model.