Role of aging in the development of metabolic dysfunctions

Contact: Dr. Annika Höhn

Funding: DZD, DFG

This research focus investigates how the aging process and associated cellular changes impact on the development of metabolic dysfunctions. We focus on redox status, proteostasis, and how cellular senescence affects the function of aging pancreatic beta cells, but also changes in aging white adipose tissue and the effects of hypercaloric diets on metabolism in different model systems. Biochemical, immunohistochemical and molecular biological investigation methods are used to fulfill these tasks. Investigating the influence of dietary interventions on metabolism as well as inflammatory status in different age groups is a main focus of our department.

Furthermore, we investigate how accumulating protein aggregates affect cellular functionality. Here we focus on the amorphous, age-dependent protein aggregate lipofuscin, found in postmitotic tissues, but also in cells with a low division rate such as pancreatic beta cells. To verify in vivo observed age-associated changes in Langerhans islets and beta cells different cell culture models are available. Furthermore, we are investigating the effects of lipofuscin on metabolism, the composition of this aggregate under different metabolic conditions in different tissues, and its proteolytic resistance. These investigations will also be extended to human lipofuscin.

Aging influences the metabolism of numerous tissues, such as skeletal and cardiac muscles, fatty tissue, skin and intestinal tissue. Some of these effects are mediated by modified proteins known as advanced glycation end products (AGEs). In order to better understand the role of AGE-modified proteins in cellular aging of these tissues, we are specifically looking for the molecular mechanisms by which AGEs influence metabolic pathways/metabolic processes. The AGE-modified proteins often assemble into protein aggregates. Some diseases, such as type 2 diabetes, are associated with increased AGE formation. Our goal is to investigate the role of AGE formation in the pathogenesis of diabetes. How AGE modification affects the nutrition and nutritional value of proteins is also being studied by the department.