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It is well-established that females live longer than males. Paradoxically, women tend to have poorer health, a condition often named sex frailty. The aim of this study was to evaluate possible frailty predictors in older mice in a sex-specific manner, in order to employ these predictors to follow-up therapy efficiency. To further evaluate therapy effects, we also investigated the use of neurotrophic insulin-like growth factor 1 (IGF-1) gene therapy and its correlation with the expression of this frailty and emotional behaviour. In order to evaluate frailty, we employed two different approaches. We performed a frailty assessment through a 31-Item Clinical Frailty Index and through a Performance-Based 8-Item Frailty Index. Our results show that both indexes are in concordance to evaluate sex differences, but they do not correlate when evaluating IGF-1 therapy effects. Moreover, in order to reduce test-to-test variability for measures of dependent variables, we compared open field results across studies assessing sex and treatment by means of the z-score normalization. The data show that regular open field parameters submitted to z-score normalization analysis could be a useful tool to identify sex differences in ageing mice after growth factor therapies. Taking this into account, sex is a factor that influences the incidence and/or nature of all major complex diseases; the main outcome of our investigation is the development of an efficient tool that compares the use of different frailty index calculations. This represents an important strategy in order to identify sex differences and therapy efficiency in ageing models., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)