Vilchez, David - C 14
Defining Cold-induced Pathways to Prevent Aging and Age-related Diseases

Prof. Dr. David Vilchez
Institute for Integrated stress Response Signaling
CMMC - PI - C 14
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Institute for Integrated stress Response Signaling
Joseph-Stelzmann-Str. 26
50931 Cologne
Introduction
Ageing is associated with changes in various cellular pathways, leading to tissue deterioration and pathological conditions, including neurodegenerative diseases characterized by protein aggregation. Thus, discovering interventions that delay aging can greatly benefit our ever-aging society. In addition to the gradual loss of physiological integrity in somatic cells such as neurons, aging also impairs germline function, reducing fertility across species. However, many lifespan-extending interventions come at the cost of reduced fertility.
Unlike other longevity interventions, our recent findings demonstrate that moderate cold temperature not only extends lifespan and prevents age-related diseases but also prolongs reproductive capacity. This presents a unique and timely opportunity for aging research. In this project, we will define cold-induced mechanisms and explore their potential application at normal and warmer temperatures to delay aging and prevent diseases while simultaneously extending fertility. Here, we will investigate how cold temperature enhances proteostasis to maintain proteome integrity and prevent pathological protein aggregation and reproductive aging. To this end, we will combine a multi-omics approach with genetics in the nematode Caenorhabditis elegans and disease modeling using patient derived iPSCs.
Clinical Relevance
Our aging population presents a major challenge due to the rising prevalence of age-related diseases and disabilities. In this project, we will define cold-induced mechanisms and explore their application at normal and warmer temperatures to identify interventions that extend healthspan and fertility. Our findings could have broad implications for multi-disease prevention and offer substantial benefits to our aging society, contributing to a sustainable understanding of age-related diseases.
Approach
- Patient-derived iPSCs culturing and differentiation into neurons
- C. elegans: aging and proteotoxic stress
- Amyotrophic lateral sclerosis and Huntington’s disease models C. elegans models
- RNAi
- CRISPR/Cas9
- Proteomics
- Co-Immunoprecipitation and interactome assays
- Western blot
- Quantitative PCR
- RNA sequencing
Project-Relevant Publications
- S. Koyuncu*, Y. Dominguez-Canterla, R. Alis, N. Salarzai, D. Petrovic, N. Flames, and D. Vilchez* (2025). The aging factor EPS8 induces disease-related protein aggregation through RAC signaling hyperactivation. Nature Aging: doi.org/10.1038/s43587-025-00943-w. *Co-corresponding authors.
- S. Bilican, Y. Nabawi, W.H. Zhang, D. Petrovic, M. Wehrmann, S. Muñoz-Garcia, S. Koyuncu, and D. Vilchez (2025). C9orf72 ALS-causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules. FEBS Letters: https://doi.org/10.1002/1873-3468.70156
- H. Alirzayeva, R. Loureiro, S. Koyuncu, F. Hommen, Y. Nabawi, W.H. Zhang, T.T.P. Dao, M. Wehrmann, H.J. Lee, and D. Vilchez (2024). ALS-FUS mutations cause abnormal PARylation and histone H1.2 interaction, leading to pathological changes. Cell Reports43:114626.
- E. Llamas, S. Koyuncu, H.J. Lee, M. Wehrmann, R. Gutierrez-Garcia, N. Dunken, N. Charura, S. Torres-Montilla, E. Schlimgen, A.M. Mandel, E. Boelen-Theile, J. Grossbach, P. Wagle, B. Schermer, T. Benzing, A. Beyer, P. Pulido, M. Rodriguez-Concepcion, A. Zuccaro, and D.Vilchez (2023).In planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation. Nature Aging3: 1345-1357 (cover).
- H.J. Lee, H. Alirzayeva, S. Koyuncu, A. Rueber, A. Noormohammadi, and D. Vilchez (2023). Cold temperature extends longevity and prevents disease-related protein aggregation through PA28γ-induced proteasomes. Nature Aging 3: 546-566.
- R. Gutierrez-Garcia, S. Koyuncu, F. Hommen, S. Bilican, H.J. Lee, A. Fatima, and D. Vilchez (2023). G3BP1-dependent mechanism suppressing protein aggregation in Huntington’s models and its demise upon stress granule assembly. Human Molecular Genetics 32: 1607-1621.
- S. Koyuncu, R. Loureiro, H.J. Lee, P. Wagle, M. Krueger and D. Vilchez (2021). Rewiring of the ubiquitinated proteome determines ageing in C. elegans. Nature 596: 285-290.
- G. Calculli, H.J. Lee, K. Shen, U. Pham, M. Herholz, A. Trifunovic, A. Dillin and D. Vilchez (2021). Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of C. elegans. Science Advances 7: eabg3012.
- H.J. Lee, A. Noormohammadi, S. Koyuncu, G. Calculli, M. Simic, M. Herholz, A. Trifunovic and D. Vilchez (2019). Prostaglandin signals from adult germline stem cells delay somatic ageing of Caenorhabditis elegans. Nature Metabolism1: 790-810 (cover).
Lab Website
For more information (research, lab members etc.), please check Vilchez Lab.
Affiliations
- Institute for Integrated Stress Response Signaling, Faculty of Medicine, University Hospital Cologne
- Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
- Institute for Genetics, University of Cologne
- Center for Molecular Medicine Cologne (CMMC)
- CRC 1678
Publications generated during 1/2026-12/2028 with CMMC affiliations
2026
Content will be made available as soon as possible.
