Aging is a universal trait among all organisms. From a public health perspective, with aging comes an increased risk of disease, including Alzheimer’s, cancer and metabolic disease/type II diabetes.
Dr. Vilchez (right) and Dr. Koyuncu examining a C. elegans sample.
Dr. David Vilchez heads a lab at CECAD, (Cellular Stress Responses in Aging-Associated Diseases), at the University of Cologne, Germany. His group has recently published research using the nematode worm, C. elegans, and their ZEISS Axio Zoom.V16 microscope on impactful topics including new regulators of lifespan and links between healthy reproductive systems and lower risk of some age-related diseases. We spoke with Dr. Vilchez to learn a bit more.
Tell us about your lab.
My lab is formed by a team of enthusiastic biologists that seek to understand how protein homeostasis (proteostasis), post-transcriptional modifications, epigenetic alterations, and cell non-autonomous responses modulate stem cell function, organismal aging, and the onset of age-related neurodegenerative diseases. We seek to uncover mechanisms of regeneration and health span extension. To address this ambitious task, we use an innovative approach that combines patient-derived induced pluripotent stem cells (iPSCs), genetics in the model organism C. elegans and state-of-the-art proteomics.
Fluorescence stereo zoom microscopy to study aging in C. elegans. Left: Muscle actin cytoskeleton in young worms. Center: Muscle actin cytoskeleton in old worms, showing destabilization of muscle cytoskeleton during aging. Right: We could prevent destabilization of muscle cytoskeleton in old worms by lowering the age-dysregulated high levels of EPS-8, a regulator of actin cytoskeleton.
What are the “big questions” your lab is seeking to address?
Top: Mitochondria in healthy muscle of C. elegans. Bottom: Fragmented mitochondria in the muscle after induction of aggregation of proteins in the germline. Imaged using ZEISS Axio Zoom.V16 microscope.
Human life expectancy has risen remarkably and the number of older people will continue to increase.
This demographic revolution presents a challenge from the increasing prevalence of age-related disorders, including neurodegenerative diseases such as Alzheimer’s that remain incurable.
Our lab applies novel approaches to understand the aging process so we can identify mechanisms to improve the quality of life when we age and prevent age-related diseases.
We use the ZEISS Axio Zoom.V16 microscope to visualize fluorescence proteins in C. elegans disease models or during the aging process in a living animal.
We saw your two recent, fascinating papers, both using C. elegans and stereo zoom microscopy. Tell us about them.
In our Nature paper, we show that the small protein ubiquitin plays an important role in the regulation of the aging process. Ubiquitin was previously known to control numerous processes, such as signal transduction and metabolism. We performed a comprehensive quantitative analysis of ubiquitin signatures during aging in C. elegans – called ubiquitin proteomics – which measures all changes in ubiquitination of proteins in the cell. The resulting data provide site-specific information and define quantitative changes in ubiquitin changes across all proteins in a cell during aging. In doing so, we discovered new regulators of lifespan and provided a comprehensive data set that helps to understand aging and longevity.
We used ZEISS Axio Zoom.V16 to image the cytoskeleton in filamentous actin with phalloidin, myosin heavy chain tagged to GFP and fluorescently tagged endogenous proteins of the intestine such as IFB-2 in C. elegans. These data were used to define how aging impairs the muscle cytoskeleton and the integrity of the intestine in these animals, and identified mechanism to prevent these alterations.
S. Koyuncu et al., Rewiring of the ubiquitinated proteome determines ageing in C. elegans. Nature 2021
G. Calculli et al. Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of C. elegans. Science Advances 2021
In our paper in Science Advances, we found that a healthy reproductive system can prevent disease-related protein accumulation in distant tissues, such as neurons, and alteration of mitochondria.
An imbalance of proteins, for example an aggregation of damaged proteins in brain cells, can lead to diseases like Alzheimer’s, Huntington’s disease or Amyotrophic Lateral Sclerosis (ALS).
Using C. elegans, we discovered that when the germline accumulates damaged protein aggregates, it releases specific signals (Wnt signaling) which in turn induce changes in mitochondria, leading to protein aggregation in other tissues such as muscle or neurons.
We used ZEISS Axio Zoom.V16 to image C. elegans germ line cells and mitochondrial morphology to look at protein aggregation during aging.
Where is your research going next?
We will now apply our recent findings on ubiquitin modifications to identify novel mechanisms that can prevent age-related diseases that remain incurable such as amyotrophic lateral sclerosis and Huntington’s disease. We will also seek to understand how the reproductive system communicates with neurons to regulate protein aggregation in these cells.