Improving our understanding of sex-dependent mechanisms regulating healthspan through novel methodological approaches

Improving our understanding of sex-dependent mechanisms regulating healthspan through novel methodological approaches Alessandra Berry1, Carla Raggi1, Chiara Musillo1, Gaia De Cristofaro1, Igor Branchi1, Silvia Poggini1, Aurelia Viglione1, Francesca Cirulli1 1Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy A well-described clinical phenomenon is that females live longer but tend to experience greater levels of co-morbidity and disability than males, a condition that has been regarded as the “frailty paradox”. Frailty is a common condition associated with ageing relying on an increased vulnerability including decline of physical conditions in addition to metabolic and cognitive impairment. Notwithstanding this evidence, standardized measures of frailty in the ageing population (and in animal models) are still lacking. In the framework of the European project “Ageing with Elegans”, we sought to device a comprehensive protocol to assess frailty in both male and female mice. A frailty index was adapted from previously published protocols. Motor coordination and balance were assessed by means of the rotarod and beam walking tests, while muscle strength was measured using the grip strength test. Specific protocols were developed to measure cognitive performance, emotionality and motivation in the automated IntelliCage (TSE, Germany). This apparatus allows testing mice in their home-cage avoiding social isolation and the experimenter’s manipulation, markedly reducing the stress imposed by testing, a condition to which old animals are highly sensitive. Using this testing battery, we found that, despite females appeared in worst physical condition than males, they showed better performance in most of the above-described tasks, in agreement with the gender differences described in the human population. In conclusion, this protocol may be applied to better characterize the age-related frailty condition and to devise specific interventions. Support: H2020 AwE (grant N. 633589).