Final Report Summary - AGEINGSTEMCELLFATE (The Role of Ectopic Adipocyte Progenitors in Age-related Stem Cell Dysfunction, Systemic Inflammation, and Metabolic Disease)
The main conclusion from this work can be summarized in the recognition that aging affects cell-intrinsic processes within different types of stem cells. However, the microenvironment also provides beneficial as well as pathogenic signals that determine stem cell fate and function. Accordingly, several secreted signals were identified that may in the future be targeted to develop strategies to combat age-related degenerative diseases. The most prominent example is a molecule known as DPP4 (Dipeptidyl-peptidase-4), which is secreted from bone-resident adipogenic cells and impairs bone fracture healing. Inhibition of DPP4 with a well-known drug class used to treat diabetes, the Gliptins, may also be employed in this novel application to treat bone disorders that are associated with excess accumulation of fat cells.
Among the common molecular mechanisms impaired in all tissues during aging, the extracellular matrix was identified. The matrix provides a scaffold for tissue-resident stem cells and its dysfunction may thereby indirectly affect regeneration. This observation has been confirmed, for instance in aging brown adipose tissue as well as skeletal muscles. In summary, the results from this project provide several new insights in the area of adipocyte biology and its interaction with tissue-specific regeneration processes that could be further developed to attenuate detrimental processes associated to aging.