Prof. dr. Riekelt Houtkooper

Professor of Translational Metabolism – Laboratory Genetic Metabolic Diseases – Amsterdam UMC(location AMC)

https://www.amsterdamumc.org/research/researchers/riekelt-h.-l.-houtkooper.htm

Topic

Metabolic regulation of aging and age-related diseases

The focus of my group’s work is on molecular and translational aspects of metabolism, and how this contributes to health and disease. On the one hand, we study rare inherited metabolic diseases such as long-chain fatty acid oxidation disorders, lysosomal storage disorders, and gyrate atrophy of the choroid and retina. On the other hand, we study metabolic dysregulation that underlies age-related pathology. We find that both rare inherited metabolic diseases and aging can have overlap in both their mechanisms (e.g. fatty acid oxidation deficiency) and their clinical manifestations (e.g. heart failure and arrhythmias), and can therefore fuel mechanistic hypotheses for one another. Furthermore, we investigate how changes in mitochondrial function impact lifespan regulation in C. elegans, and how these mechanisms are conserved in mammalian cell and animal models. Specifically, we elucidated how mRNA translation and mitochondrial fusion/fission are functionally involved in lifespan and healthspan management (e.g. Cell Metabolism 2020, JCB 2020). Moreover, we found a marked dysregulation in complex lipid metabolism that we are currently following up with functional validation experiments in human clinical samples. Collectively, our research is geared to identify novel therapies to promote metabolic health in humans. We recently identified a novel NAD precursor, which has high potential for translation to pre-clinical disease models in which NAD metabolism is compromised (e.g. FASEB 2021). To identify novel therapeutics, we use knowledge on age-related pathways and in silico drug screening and machine learning approaches.

Main aims

• Exploring the interplay between mitochondrial (dys)function and aging
• Understanding how complex lipid biology contributes to age-related health
• Metabolic biomarkers of aging and age-related disease
• NAD metabolism and NAD precursor supplementation in health and disease
• Fatty acid oxidation deficiency in relation to cardiac and muscle health

Methodology

Metabolomics, lipidomics, fluxomics, multi-omics data integration, respirometry, metabolic enzyme assays, in silico drug screening, cell culture drug assays, C. elegans lifespan and healthspan

Funding

• NWO-VIDI
• ERare
• Amsterdam UMC