A5038636084- Genetics, Aging, and Longevity in Model Organisms
- Spaceflight effects on biology
- Circadian rhythm and melatonin
- Bioinformatics and Genomic Networks
- Neuroendocrine Tumor Research Advances
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Cellular Mechanics and Interactions
- Lung Cancer Research Studies
- Neuroblastoma Research and Treatments
- Physiological and biochemical adaptations
- Genomics and Chromatin Dynamics
- Genomics, phytochemicals, and oxidative stress
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- thermodynamics and calorimetric analyses
- Protein Tyrosine Phosphatases
- Chromosomal and Genetic Variations
- Advanced Proteomics Techniques and Applications
- 3D Printing in Biomedical Research
- Enzyme Structure and Function
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Connective tissue disorders research
- Heat shock proteins research
ETH Zurich
2015-2024
Board of the Swiss Federal Institutes of Technology
2019-2024
Matrix Research (United States)
2021
Department of Medical Sciences
2020
Bioengineering (Switzerland)
2015
Abstract Inhibition of the master growth regulator mTORC1 (mechanistic target rapamycin complex 1) slows ageing across phyla, in part by reducing protein synthesis. Various stresses globally suppress synthesis through integrated stress response (ISR), resulting preferential translation transcription factor ATF-4. Here we show C. elegans that inhibition or increases ATF-4 expression, and mediates longevity under these conditions independently ISR signalling. promotes activating canonical...
Abstract Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact gene expression. However, the role of composition changes in healthy remains unclear. Here we perform proteomics in-vivo monitoring systematically investigate (matreotype) during C. elegans revealing three distinct collagen dynamics. Longevity interventions slow stiffening prolong...
Proteins are the building blocks of life. While proteins and their localization within cells sub-cellular compartments well defined, predicted to be secreted form extracellular matrix - or matrisome remain elusive in model organism C. elegans. Here, we used a bioinformatic approach combining gene orthology protein structure analysis an extensive curation literature define elegans matrisome. Similar human genome, found that 719 out ~20,000 genes (~4%) genome encodes proteins, including 181...
The identification and validation of drugs that promote health during aging ("geroprotectors") are key to the retardation or prevention chronic age-related diseases. Here, we found most established pro-longevity compounds shown extend lifespan in model organisms also alter extracellular matrix gene expression (i.e., matrisome) human cell lines. To harness this observation, used age-stratified transcriptomes define matreotype, which represents matrisome pattern associated with age. Using a...
Abstract Repurposing drugs capable of extending lifespan and health span has a huge untapped potential in translational geroscience. Here, we searched for known compounds that elicit similar gene expression signature to caloric restriction identified rilmenidine, an I1‐imidazoline receptor agonist prescription medication the treatment hypertension. We then show treating Caenorhabditis elegans with rilmenidine at young older ages increases lifespan. also demonstrate stress‐resilience, span,...
Human centenarians and longevity mutants of model organisms show lower incidence rates late-life morbidities than the average population. However, whether is caused by a compression portion life spent in state morbidity,
Little is known about the possibility of reversing age-related biological changes when they have already occurred. To explore this, we characterized effects reducing insulin/IGF-1 signaling (IIS) during old age. Reduction IIS throughout life slows decline in diverse species, most strikingly nematode Caenorhabditis elegans. Here show that even at advanced ages, auxin-induced degradation DAF-2 single tissues, including neurons and intestine, still able to markedly increase C. elegans lifespan....
Herein we demonstrate the segmentation of alginate solution streams to generate fibers precisely controllable lengths between 200 and 1000 μm.
Extracellular matrices are essential for cellular and organismal function. Recent genome-wide phenome-wide association studies started to reveal a broad spectrum of phenotypes associated with genetic variants. However, the phenome or all variants in extracellular matrix genes is unknown. Here, we analyzed over two million recorded genotype-to-phenotype relationships across multiple species define their phenomes. By using previously defined matrisomes humans, mice, zebrafish,
Abstract Significant non‐genetic stochastic factors affect aging, causing lifespan differences among individuals, even those sharing the same genetic and environmental background. In Caenorhabditis elegans , in heat‐shock response (HSR) are predictive of lifespan. However, contributing to heterogeneity HSR still not fully elucidated. Here, authors characterized dynamics isogenic C. expressing GFP reporter for hsp‐16.2 identifying key contributors heterogeneity. Specifically, microfluidic...
The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and aging. analysis of these possible with the GWAS PheWAS methodologies, through our analysis, we aimed to explore relationships between polymorphisms compendium ECM genes (i.e., matrisome genes) various states. A significant contribution on part evident types disease, particularly those core-matrisome genes. Our results confirm previous links connective-tissue disorders but also unearth new...
Abstract There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced GEP-NEN patients applied this model targeted rapid ex vivo pharmacotyping, next-generation sequencing, perturbational profiling. used tissue-matched PD to profile individual patients,...
Abstract The Structural Maintenance of Chromosomes (SMC) complexes, cohesin and condensins, are named for their roles in separating compacting chromosomes during meiosis mitosis. Recent data from mammalian cells have revealed additional functions cohesin, including folding the interphase genome into loops domains. However, it remains unclear what determines holocentric species. To address this question, we systematically acutely inactivated each SMC complex. Surprisingly, found that,...
Abstract The identification and validation of drugs that promote health during aging (‘geroprotectors’) is key to the retardation or prevention chronic age-related diseases. Here we found most established pro-longevity compounds shown extend lifespan in model organisms also alter extracellular matrix gene expression ( i.e., matrisome) human cell lines. To harness this novel observation, used age-stratified transcriptomes define matreotype, which represents matrisome pattern associated with...
Although genetic approaches have identified key genes and pathways that promote longevity, systems-level are less utilized. Here, we took advantage of the wealth omics data characterizing BXD family mice. We associated transcript peptide levels across five tissues from both female male isogenic lines with their median lifespan. over 5000 showed a longevity correlation in given tissue. Surprisingly, found than 1% overlap among longevity-correlating sex. These shared consist 51 genes, which 13...
Abstract Inhibition of the master growth regulator mTORC1 (mechanistic target rapamycin complex 1) slows ageing across phyla, in part by reducing protein synthesis. Various stresses globally suppress synthesis through integrated stress response (ISR), resulting preferential translation transcription factor ATF-4. Here we show C. elegans that inhibition or increases ATF-4 expression, and mediates longevity under these conditions independently ISR signalling. promotes activating canonical...
ABSTRACT Systems biology approaches often use inferred networks of gene expression and metabolite data to identify regulatory factors pathways connected with phenotypic variance. Generally, study-specific multi-layer “Omics” datasets are used contextualize generic molecular networks. In this regard separating upstream causal mechanisms, downstream biomarkers, incidental correlations remains a significant challenge, yet it is essential for designing mechanistic experiments. To address this,...
Abstract Although it is postulated that dysfunctional extracellular matrices (ECM) drive aging and disease, how ECM integrity assures longevity unknown. Here, using proteomics in-vivo monitoring of fluorescently tagged proteins, we systematically examined the composition during Caenorhabditis elegans revealing three distinct collagen dynamics. We show age-dependent stiffening inert was slowed by interventions through prolonged replenishing collagens. In genetic automated lifespan screens for...
Abstract There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous epithelial malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced GEP-NEN patients applied this model targeted rapid ex vivo pharmacotyping, next-generation sequencing, perturbational profiling. used tissue-matched PD to profile...
Abstract The extracellular matrix (ECM) is a pivotal three-dimensional network crucial for tissue organization, cellular communication, and fundamental processes, where collagens are the major chemical entity in amount. ECM deregulation directly involved with several pathologies, such as tumour growth invasiveness, atherosclerosis, diabetic nephropathy. Mutations von Hippel-Lindau suppressor (pVHL) cause VHL syndrome, multi-tumour syndrome commonly associated clear cell renal carcinoma...