Researchers are developing mathematical tools to measure how quickly cellular proteins are broken down, providing new insights into aging and disease. Their research classifies proteins into three degradation rate groups and examines their effects on muscle growth, starvation, and neurodegenerative diseases. This method improves our understanding of cellular processes.

New mathematical methods that reveal the rate at which cellular proteins degrade could offer a deeper understanding of the aging process, according to a recent study co-authored by a Mississippi State researcher with colleagues from Harvard Medical School and the University of Cambridge.

Galen Collins, Associate Professor at the Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology at Moscow State University, is a co-author of a groundbreaking paper published in 2014. Proceedings of the National Academy of Sciences In April

“We already understand how fast proteins form, which can happen in minutes,” said Collins, who is also a scientist at the Mississippi Agricultural and Forestry Experiment Station. “Until now, we had a very poor understanding of how long it would take for them to fail.”

An Applied Mathematics paper presents new tools to measure the decay rate of cellular proteins (how quickly they break down), helping us understand how cells grow and die and how we age. Proteins, complex molecules made up of different combinations of amino acids, carry most of the workload within the cell, providing structure, responding to messages from outside the cell, and removing waste.

New discoveries regarding protein degradation rate

The results showed that not all proteins are degraded at the same rate, but instead fall into one of three categories that break down over minutes, hours, or days. While previous studies have examined cellular protein breakdown, this study is the first to measure the rate at which all cellular protein molecules are broken down using a technique called maximum entropy.

“For certain types of scientific questions, experiments can often reveal an infinite number of possible answers, but not all of them are equally plausible,” says lead author Alexander Deer, a research associate in applied mathematics at Harvard University. “The maximum entropy principle is a mathematical law that shows us exactly how to calculate the probability (‘entropy’) of each answer so that we can choose the most likely one.”

“This math is like a camera zooming in on your license plate from a distance and determining what the numbers should be,” Collins said. “Maximum entropy gives us a clear and precise picture of how protein degradation occurs in cells.”

Consequences of protein degradation

The team also used these tools to study some specific consequences of protein degradation in humans and animals, primarily investigating how these parameters change as muscles develop and adapt to fasting.

“We found that fasting had the greatest effect on a group of intermediate proteins in muscle cells with a half-life of several hours, leading to a shift and acceleration of decay,” Collins said. “This finding may have implications for cancer patients who experience cachexia, or muscle wasting, due to the disease and its treatment.”

They also investigated how altering the breakdown of certain cellular proteins contributes to neurodegenerative diseases.

“These diseases occur when used proteins, which normally break down quickly, live longer than they should,” Collins said. “The brain becomes like a teenager’s bedroom, accumulating garbage and becoming uninhabitable if you don’t clean it out.”

Dear confirmed that the value of the study lies not only in the fact that it reveals the degeneration of cellular protein, but also in the fact that scientists have obtained a new method to accurately study the activity of cells.

“Our work provides a powerful new experimental method for measuring protein metabolism in cells,” he said. “Its simplicity and speed make it particularly suitable for studying metabolic changes.”

Collins’s doctoral advisor at Harvard and co-author of the paper, the late Alfred Goldberg, was a pioneer in the study of protein life and death. Collins noted that the research builds on Goldberg’s nearly five decades of research and his late-career collaborations with mathematicians at the University of Cambridge. After arriving at MSU a year ago, Collins continued to work with his colleagues to finish the work.

“It is an incredible honor to be published in this magazine. PNAS“But it’s also been a lot of fun to be a part of this team,” Collins said. “And it’s been a big deal to see my former mentor’s work completed and published.”