Grant: Project Grant

Global gains in life expectancy allow current generations to enjoy many extra healthy and active years. However, aging is also associated with a higher incidence of disease, which severely affects the quality of life and increases pressure on healthcare systems. Declining skeletal muscle (SkM) mass and function coupled with a reduced tissue healing capacity is one of the main drivers of loss of independence in the elderly. SkM tissue is highly complex and composed of a wide range of different cell types. Up to date, it remains unclear which cell types in SkM are most susceptible to aging and how age-induced dysfunction in these cellular compartments affects the maintenance and healing capacity of the tissue. Here we propose to model the impact of aging on the different cell populations in SkM using a range of novel and innovative mouse models. These models allow us to induce accelerated aging restricted to certain cell populations in SkM so that we can interrogate effects on tissue composition, function and regeneration. For the first time, this approach will allow us to identify the cell populations that represent the main "drivers" of SkM aging. We also propose to investigate a novel cell-therapy based approach that can restore the youthful function of cellular compartments involved in muscle aging. Lastly, we will evaluate the systemic application of growth factors controlling driver cell function for therapeutic efficiency in rejuvenating SkM tissue in aged mice. Our work will not only provide fundamental insights into the biology of SkM tissue but will also lay the foundation for the development of much needed therapeutic interventions for SkM aging and its associated pathologies.