Muscle health
The PPS muscle health was a collaboration between different partners with the primary aim to identify underlying mechanisms of muscle weakness in the elderly (sarcopenia) and to demonstrate potential male-female differences.
Age-related loss of muscle mass and strength, or sarcopenia, is a fundamental cause of frailty, functional decline and disability, and represents a huge potential public health problem worldwide with major implications for healthcare costs. The insight into the underlying mechanisms and potential male-female differences that was obtained in this TKI project is essential for the identification of potential new targets for therapies and the development of effective (and potentially stratified) interventions for sarcopenia.
In this TKI project, existing muscle and blood samples from a human study were used in which vulnerable elderly with muscle weakness were compared with healthy elderly and healthy young people. New histopathological imaging analyses for muscle tissue were developed as well. In addition, a novel bioinformatic approach was used to identify candidate biomarkers that were then subsequently validated using blood samples. Finally, a number of preclinical mouse models for muscle weakness were compared with human sarcopenia to determine the overlapping features.
While we found that for healthy muscle aging the changes were largely shared between males and females, the changes associated with physical weakness in the elderly groups were rather sex-specific. These data suggested that the underlying mechanisms in the development of frailty are not merely a continuum or more severe form of aging, but rather has unique pathways that are sex-specific. Furthermore, the project revealed 2 gender-specific biomarkers for vulnerability (i.e. 2 for women and 2 for men). Lastly, a translational mouse model (combination of caloric restriction & partial immobilization) was developed that adequately mimicked the underlying physiological pathways of sarcopenia, making it a valuable tool for screening pharmacological and lifestyle interventions.
