Metabolische Kontrolle von Altern und Krankheit

Healthy aging and novel strategies for the prevention of age-associated disease are among the most demanding societal challenges today. Fortunately, global life expectancy is steadily increasing; however, the prevalence of chronic diseases rises significantly with age. This is largely due to the age- related loss of metabolic control and hence the loss of precise and flexible regulation of the metabolism. The Cluster of Excellence MetAGE is an interdisciplinary network of researchers from the University of Graz, the Medical University of Graz, and the Medical University of Vienna. In MetAGE, researchers investigate metabolic regulation of healthy aging and the age-related loss of metabolic control, which is mechanistically still poorly understood. MetAGE focuses on studying seven key factors of metabolic control: (1) Processes that regulate the balance of lipid metabolism and fat distribution in the body - the so-called lipostasis; (2) processes related to the balance of protein synthesis, quality control and degradation - the so-called proteostasis; (3) the role of natural polyamines and their metabolism, which is associated with accelerated aging processes when impaired, while their supplementation extends the health and lifespan of model organisms; (4) the function of mitochondria - the powerhouses of cells - which play a central role in energy production and regulation of metabolism, while their impaired function is associated with the aging process; (5) the communication axis between the brain and other organs that plays a crucial role in body weight regulation and metabolic flexibility; (6) chronic, subclinical inflammatory processes and the immune system, whose function deteriorates with age; and (7) the influence of sex and sex hormones on metabolic health and aging. A unique characteristic of MetAGE is the close integration of laboratory experiments, model organisms, and clinical trials in humans. This involves establishing close and direct communication between the preclinical research program and a clinical trial program to ensure translation of findings from basic research to human aging. In the course of MetAGE, establishment of the Healthy Aging Center Austria will ensure high quality and internationally visible translational aging research in Austria that goes beyond the project period of MetAGE. The preclinical and clinical research results generated by MetAGE will contribute to (i) a better understanding of the age-related loss of metabolic control, (ii) the development of nutritional interventions and fasting regimes that support the restoration of metabolic control, and (iii) pave the road for pharmaceutical interventions and development of novel drugs, all aimed at extending the healthy lifespan.