Goal of our research is to aid the discovery of aging-preventive interventions. We do this by the following approaches:
1) Study of aging-regulatory mechanisms in C. elegans
We know that aging is a plastic, highly regulated process, but our understanding of the mechanisms that confer this regulation is incomplete. Detailed knowledge of these mechanisms will be crucial for any educated aging-preventive approaches. Thus the main effort of our lab is their discovery and further exploration. We conduct most of this work in the model organism Caenorhabditis elegans. This organism is ideal for aging-related research, as it is technically well established, short-lived (allowing for lifespan as an easily measurable age-related phenotype), and very responsive to alterations in its aging-regulatory pathways. The laboratory combines biochemistry (Proteomics, ChIP-Seq,…) and transcriptomics (mRNA-Seq) with high-throughput genetic screening approaches (RNAi, forward genetics,...), to understand the regulation of aging at molecular and mechanistic resolution.
Recently, we have focused on the mechanistic exploration of lifespan regulatory transcription factors, in particular DAF-16(FOXO) – a central driver of longevity that integrates many lifespan extending stimuli, i.e. nutrient deprivation, various stresses, or cues of infertility to confer transcription of a wide range of stress resistance and longevity determining genes. This work is complemented by studies on the role of chromatin states, chromatin remodelers, and the epigenome in the context of aging and age-related disease.
2) Search for aging-preventive interventions in humans
In addition to the mechanistic studies from above, we also seek pharmacological interventions against aging directly in mammalian systems, including humans. For this, we validate aging-regulatory mechanisms of particular appeal that were identified in simpler model organisms and test possible targeting strategies. Further, we develop mammalian screening methodologies that allow for the identification of aging-preventive compounds.
- Lezzerini, M., Riedel, C.G. (2016) ATP-dependent chromatin remodeling: from development to disease. Book Chapter in “Chromatin Regulation and Dynamics”, Elsevier, ISBN: 978-0-12-803395-1.
- Riedel, C.G. et al. (2013) DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity. Nature Cell Biology, 15, 491-501.
- López-Otín, C., Blasco, M.A., Partridge, L., Serrano, M., Kroemer, G. (2013) The hallmarks of aging. Cell 153, 1194-217.
- Feser, J., & Tyler, J. (2011) Chromatin structure as a mediator of aging. FEBS letters, 585(13), 2041–8.
- Calnan, D.R. & Brunet, A. (2008) The FoxO code. Oncogene 27, 2276-88.
- Kenyon, C. (2005) The plasticity of aging: insights from long-lived mutants. Cell 120, 449-60.