Ageing – basic mechanisms and interventions – Christian Riedel's research group

Ageing and age-related diseases are central to human health

Photo of a man
Christian Riedel

Our health and longevity is largely determined by the rate at which we age. Fortunately, ageing 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 ageing-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 ageing-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.

Projects

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 remodellers 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.

Other projects

We are also interested in stress responses in the context of cancer. And as part of a collaboration with the teams of Sarah Hägg and Per Nilsson, both at Karolinska Institute, we work on the repurposing of FDA-approved drugs for treatment or prevention of Alzheimer’s disease.

Further reading:

Janssens, G.E., Lin, X.X., Millan-Arino, L., Sen, I., Kavsek, A., Seinstra, R.I., Stroustrup, N., Nollen, E.A.A., Riedel, C.G. (2019) Transcriptomics-based screening identifies pharmacological inhibition of Hsp90 as a means to defer aging. Cell Reports 27: 467-480.

Lin, X.X., et al. (2018) DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity. Nature Communications 9(1): 4400.

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.

Publications

Selected publications

Funding

Christian Riedel’s group is grateful for support by Vetenskapsrådet, Cancerfonden, Karolinska Institutet, Novo Nordisk Foundation (DK), National Institutes of Health (USA), Impetus Grants and the pharmaceutical company AstraZeneca.

Staff and contact

Group leader

All members of the group

Alumni

Hadi Bazzi, Master Student

Ashwini Jatti, Master Student

Sascha Boma Okendi, MSc

Robert Smetana, Master Student

Maite Brachthäuser, Master Student

Ilke Sen, PhD Student/Postdoc

Lluís Millán Ariño, Postdoc

Andrea Stöhr, Postdoc

Xin Zhou, Postdoc

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

Daniel Edgar, Postdoc

Poomy Pandey, Research Assistant

Xin-Xuan Lin, PhD Student

Sonja Pikkupeura, Master Student

Hazel Ang, Postdoc

Quadri Ajibola Omotesho, Master Student

Manon Chevalier, Postdoc

Keywords:
Bioinformatics and Systems Biology (methods development, see 10203) Cell and Molecular Biology Genetics (medical, see 30107 and agricultural, see 40402)
CR
Content reviewer:
Sara Bruce
04-07-2024