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Center for Liver, Digestive and Metabolic Diseases (CLDM)

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The prevalence of obesity, diabetes, dyslipidemias, non-alcoholic liver diseases and other metabolism-related disorders increases with age and changes in lifestyle, and is emerging as a major economic and social burden. These disorders have a causal role in liver, digestive and cardiovascular diseases, cancer, and other age-related chronic diseases, and therefore are an important cause of morbidity. These disorders may have an extended subclinical course, i.e. before the actual diagnosis is made. Because treatment of the end-organ damage associated with these diseases is difficult and often leads to permanent and significant loss of quality of life, focus on prevention and early detection is crucial. Understanding the physiological, pathophysiological, and developmental basis of these diseases is necessary for the identification of interventional targets and for the design of novel evidence-based strategies to prevent, treat or deal with the consequences of these diseases.

Scientific and Societal output   Dissertations   Principal Investigators   Programme Leaders   Description of the Programme  

Because of the complexity of diseases that involve metabolism, the CLDM program requires the multidisciplinaryapproach being taken that integrates systemsbiology and computational systems biologywith basicand clinicalresearch at the organ, inter-organ, cellular, sub-cellular, and molecular level. Relevant mechanisms are studied throughout the life span, including prenatal life, in order to understand the contribution of diet and metabolic programming to these diseases. These mechanisms include the transport and processing of proteins, lipids and metabolites, as well as gene regulation and signaling networks. Cellular mechanisms are investigated with the aim of preventing and/or developing treatment strategies for age and obesity-related metabolic disorders. We generate novel hypotheses using human genetics, human cohorts/biobanking and systems biology and validate these using advanced mouse and cellular models. The program PIs contribute the necessary variety of complementary methodology and expertise.

Mission  

The mission of the program is to define the molecular basis of inborn, acquired and age-related diseases that are caused by perturbations in metabolism and/or the flow of metabolites, which often involve the liver and intestine, and to define leads for new treatment strategies. The CLDM aims to develop tools for the better prediction of the onset of metabolism-related chronic diseases and the earlier detection thereof, and to better prevent or more efficiently treat disease later on.

Relevance to Healthy Ageing  

A healthy metabolism is crucial for humans to develop from childhood to adulthood, and thereafter to age in a healthy and active way. Metabolism and the ageing process are tightly correlated: metabolism affects the ageing of an organism, while the metabolic system declines with increasing age. The prevalence of metabolic syndrome − of which obesity, hyperglycemia and dyslipidemias are core components − increases strongly with age. Furthermore, the prognosis, progression and mortality of these diseases depend in part on age. Metabolism-related and chronic diseases often display a period without clear clinical symptoms or with non-specific clinical symptoms, which means such diseases may easily go undiagnosed. Nevertheless, this is the stage in the process of ageing where we can intervene, potentially in a personalized manner. Realization of the goals set by the CLDM will lead to better detection, prevention and intervention of disease and, consequently, to a prolonged healthy life span.