Mechanisms of Aging Regulation
Aging and age-related diseases are central to human health; we study the molecular mechanisms that regulate aging and hope to exploit them for therapeutic purposes.
Our health and longevity is largely determined by the rate at which we age. Fortunately, aging is a plastic process. In our research group we use the nematode Caenorhabditis Elegans as a model systems to understand the pathways that can accelerate or impair aging. C. Elegans is ideal for aging-related research, as it is technically well established, short-lived (allowing for lifespan as an easily measurable phenotype), and very responsive to alterations in its aging-regulatory pathways.
These studies are complemented by efforts in human tissue culture, to verify human conservation and further explore our findings for therapeutic purposes. Our research combines biochemistry (Proteomics, ChIP-Seq, mRNA-Seq,…) with high-throughput genetic screening approaches (RNAi), to understand the regulation of aging at molecular and mechanistic resolution.
|Christian G. Riedel, PhD, Group Leader, e-mail: email@example.com
Lioba Körner, Master Student
Naghmeh Rajaei, Postdoc
Marco Lezzerini, Postdoc
Mengshan Liu, Master Student
Bora Baskaner, Research Assistant
Simone Brandenburg, Research Assistant
Nataly Puerta Cavanzo, Master Student
Marlies Oomen, Master Student
Irem Yücel, Bachelor Student
Tanja Iken, Bachelor Student
Georges Janssens, Postdoc
The role of DAF-16/FOXO and its cofactors in aging regulation
A current focus of ours is the mechanistic exploration of aging 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. We recently identified a variety of co-factors to DAF-16/FOXO, and now we are exploring their mechanistic role.
The role of the chromatin landscape in aging regulation
Transcription is not only controlled by transcription factors but also the chromatin landscape that they interact with. Hence we are complementing our work by studies on the role of chromatin states, chromatin remodelers and the epigenome in the context of aging and age-related disease.
Search for aging-preventive interventions in humans
In addition to the mechanistic studies from above, we also seek pharmacological interventions against aging 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.
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.
Kenyon, C. (2010) The genetics of ageing. Nature 464, 504-12.
Calnan, D.R. & Brunet, A. (2008) The FoxO code. Oncogene 27, 2276-88.
ICMC / Financial support
Christian Riedel’s group is located at and financially supported by the Integrated Cardio Metabolic Center (ICMC) at Karolinska Institutet. The ICMC has recently been established as a research collaboration between Karolinska Institutet and the pharmaceutical company AstraZeneca to address a variety of strategic research areas in the fields of cardiovascular and metabolic diseases.
In addition, the group is supported by grants from Vetenskapsrådet and Karolinska Institutet.