Ubiquitin is a crucial, small protein that is thought to be present in all eukaryotic cells and is very similar from one organism to another; the yeast and human versions of ubiquitin differ by only three amino acids. Ubiquitin plays a major role in regulating proteins; when ubiquitin is attached to a protein, it's said to be ubiquitinated, and is tagged for destruction. Damaged proteins build up during aging, and ubiquitin is known to influence the aging process because of its role in cellular quality control.
Researchers can analyze all of the proteins the are ubiquitinated in a cell, and create a ubiquitin signature for cells, or in the case of a new study reported in Nature, the model organism Caenorhabditis elegans, a nematode worm. This approach can compare the total number of proteins in a cell with how many are ubiquitinated, and how protein turnover changes during aging. The research revealed that there was an overall loss of ubiquitination during aging.
"Our study of ubiquitin changes led us to a number of exciting conclusions with important insights for understanding the aging process," said lead study author Dr. Seda Koyuncu of the CECAD Cluster of Excellence for Aging Research at the University of Cologne. "We discovered that aging leads to changes in the ubiquitination of thousands of proteins in the cell." Koyuncu added that those changes could be prevented by a reduction in both food consumption and insulin signaling.
The proteasome is a complex that destroys ubiquitinated proteins. As aging progressed in their research model, the ubiquitination process became unreliable; some proteins were not tagged with ubiquitin as often, and these defective proteins built up and caused cell death.
"Remarkably, we saw that reducing the protein levels of these untagged proteins was sufficient to prolong longevity, while preventing their degradation by the proteasome shortened lifespan," said Koyuncu.
"Our findings may point to new ways to delay the aging process and improve quality of life in old age. In particular, we have established a novel link between aging and general changes in the ubiquitin-modified proteome, a process that actively influences longevity," said study coordinator David Vilchez, a research group leader at CECAD and the Center for Molecular Medicine Cologne (CMMC).