Projekt

A hallmark of aging is the progressive loss of muscle mass and function (sarcopenia), which, in the aged, is largely responsible for the weight loss, frailty, disability and death. The dystrophin-glycoprotein complex (DGC) is vital for muscle health, and its dissociation during aging significantly contributes to the deterioration in muscle size, strength and function. In fact, dissociation of DGC seems to precede and promote age-associated muscle atrophy and reduced functional capacity. Conversely, stabilization of DGC structure markedly attenuates atrophy. Currently, there are no effective therapies for sarcopenia in humans especially because many facets of age-related atrophy are unclear. Since the DGC is highly evolutionary conserved, a novel approach is proposed to study the mechanisms regulating DGC stability during aging using both, the fruit fly Drosophila melanogaster and mouse as model organisms. Our preliminary unexpected findings reveal a novel DGC interacting component in skeletal muscle, plakoglobin, which, in cardiac muscle, is a component of adhesion complexes and is critical for tissue architecture and stability. In addition, the ubiquitin ligase Trim32 as a novel inhibitor of plakoglobin function was found. Now it will be investigated if inhibition of the key factors that promote DGC dissociation during aging (e.g. Trim32 or certain microRNAs) will enhance DGC stability and thus prevent age-related atrophy. This work will provide valuable insights into the mechanisms that promote DGC dissociation and loss of muscle mass during aging, and may facilitate the discovery of new drug targets for therapeutic intervention.

• Priv.-Doz. Dr. Halyna Shcherbata

  Max-Planck-Institut für
  biophysikalische Chemie
  Genexpression und Signalwirkung
  Göttingen
  

• Dr. Shenhav Cohen, Ph.D.

  Technion-Israel Institute of Technology
  Biology
  Haifa
  Israel