For the first time, scientists have developed a method to precisely control protein levels in various tissues of a living animal throughout its entire lifespan. This pioneering research, conducted by a team at the Center for Genomic Regulation in Barcelona and the University of Cambridge, opens new avenues for understanding the molecular mechanisms of aging and disease. The findings were published in the journal Nature Communications on December 12, 2025.
The innovative approach enables researchers to adjust protein concentrations in real-time, providing insights into how proteins interact across different tissues. The study focused on the nematode worm Caenorhabditis elegans, where scientists successfully manipulated protein levels in both the intestines and neurons. This level of control was previously unattainable with existing techniques.
Implications for Aging and Disease Research
The ability to modulate protein amounts with high accuracy will significantly impact research on aging and disease. According to Dr. Nicholas Stroustrup, the senior author of the study, “No protein acts alone. Our new approach lets us study how multiple proteins in different tissues cooperate to control how the body functions and ages.” This capacity to observe protein interactions in real-time could transform experiments aimed at understanding health maintenance and disease progression.
Traditional experimental methods often fall short in separating the effects of proteins across various body parts. The new technique addresses this limitation, allowing researchers to explore how different tissues communicate and influence aging processes. The authors highlight that previous methods lacked the precision necessary to investigate subtle variations in protein levels.
Understanding the Dual-Channel AID System
The researchers’ technique is an enhancement of the auxin-inducible degron (AID) system, originally derived from plant biology. This system utilizes the plant hormone auxin to regulate protein degradation. By attaching a degron tag to the target protein, researchers can control its stability in the presence of auxin. When auxin is absent, the protein is restored, enabling reversible control.
Through engineering different versions of the TIR1 enzyme and degrons, the team developed a “dual-channel” AID system. This advancement allows for targeted control of protein levels in multiple tissues simultaneously. For instance, scientists can manage the same protein in the worm’s intestine and neurons independently or control different proteins at once.
Another significant breakthrough is the system’s functionality in reproductive tissues, an area where AID systems typically struggle. The research team adapted their approach to ensure effective control throughout the organism, including germline cells.
Dr. Jeremy Vicencio, a postdoctoral researcher at the Center for Genomic Regulation and co-author of the study, noted the engineering challenges involved. “Getting this to work was quite an engineering challenge. We had to test different combinations of synthetic switches to find the perfect pair that didn’t interfere with one another,” he explained. The successful application of this method could lead to new experimental designs in biology.
This research signifies a substantial leap forward in the field of molecular biology, providing scientists with a powerful tool to dissect the complexities of protein interactions and their roles in health and disease. The implications for future studies on aging and systemic processes are profound, potentially reshaping our understanding of how proteins contribute to the biological functions of living organisms.
For further details, refer to the original study published in Nature Communications (2025). DOI: 10.1038/s41467-025-66347-x.
