nematode Caenorhabditis elegans
Image Credit: Scientific Frontline
Scientific Frontline: "At a Glance" Summary
- Main Discovery: A novel "aging clock" based on gene expression patterns has revealed that individual nerve cells age at varying rates, with some neurons exhibiting advanced biological aging even in young organisms.
- Methodology: Researchers analyzed the complete nervous system of the nematode Caenorhabditis elegans, employing machine learning to correlate transcriptome changes with cellular age and screen potential pharmacological interventions.
- Key Data: The study identified syringic acid (found in blueberries) and vanoxerine as agents that preserve neuronal health, while unexpectedly classifying resveratrol and WAY-100635 as neurotoxins that accelerate degeneration.
- Significance: This research isolates increased protein biosynthesis as the primary molecular driver of premature neuronal aging, offering a precise mechanism to distinguish between vulnerable and resilient neuron types.
- Future Application: Implementation of AI-driven classification systems will allow scientists to rapidly identify and repurpose drugs that specifically inhibit neuronal aging processes for human neurodegenerative therapy.
- Branch of Science: Neuroscience, Gerontology (Aging Research), and Bioinformatics.
- Additional Detail: Rapidly aging neurons displayed hyperactive protein production, and pharmacologically inhibiting this specific process was found to be sufficient to preserve the cells' structural integrity.
Using an aging clock, researchers from the University of Cologne have used the Caenorhabditis elegans model organism to demonstrate that nerve cells age differently. They identified both the causes of aging and molecules that keep the nervous system healthy in old age
The nematode Caenorhabditis elegans has a simple nervous system consisting of just 302 neurons. The human brain, with approximately 90 billion neurons, is far more complex. Nevertheless, neurons in the nematode perform functions like those of the human nervous system. This makes C. elegans a suitable model organism for studying how the brain ages. All neural connections are known, and the aging process of each individual nerve cell can be tracked throughout its lifetime.
Professor Dr Björn Schumacher, Principal Investigator at the CECAD Cluster of Excellence for Aging Research, and bioinformatician Dr David Meyer determined the age of each individual neuron of the nematode using a specially developed aging clock that can accurately predict biological age based on changes in gene expression. The study ‘Aging clocks delineate neuron types vulnerable or resilient to neurodegeneration and identify neuroprotective interventions’ was published in Nature Aging.
The researchers showed considerable differences in cell age even in young animals. Some neurons appeared to be considerably “older” than the animals themselves. Neuroscientist Dr Christian Gallrein, who now works at the Leibniz Institute on Aging - Fritz Lipmann Institute in Jena, investigated what happened to these pre-aged neurons in the young adult nematodes. They quickly showed massive degeneration, and the nerve processes degenerated in a very short time.
The production of proteins was found to be the molecular driver of neuronal aging; rapidly aging neurons had particularly active protein biosynthesis. If this process is pharmacologically inhibited, the rapidly aging neurons are well preserved. As the nematodes' neurons age in a similar way to those of the human brain, the team developed an AI-supported approach that uses machine learning to classify therapeutics according to whether they could accelerate or delay the neuronal aging process. New small molecules such as the natural plant substance syringic acid, found in blueberries and blue grapes, and the dopamine reuptake inhibitor vanoxerine were found to protect neurons from the aging process and thus keep the nervous system intact in old age. In contrast, substances such as the serotonin 5-HT1A receptor antagonist WAY-100635 and resveratrol were determined to promote the aging process and neurodegeneration and could act as neurotoxins.
“Our work has revealed the differences in the aging process of individual neurons for the first time,” says Schumacher. “This gives us completely new insights into why some neurons age early. In addition, we now have a new approach that uses machine learning to swiftly identify potential therapeutic substances. This will facilitate the development of novel treatments to preserve brain function and prevent neurodegenerative diseases in future.”
Published in journal: Nature Aging
Authors: Christian Gallrein, David H. Meyer, Yvonne Woitzat, Valeria Ramirez-Ramirez, Thanh Vuong-Brender, Janine Kirstein, and Björn Schumacher
Source/Credit: University of Cologne
Reference Number: ns020326_01