Slow proteins may support aging and chronic disease

As we age, our bodies slow down – not just in how we move, but also at the cellular level, where a decline in protein mobility can contribute to the development of chronic health issues.

Molecular stress caused by diabetes, fatty liver disease, and other chronic diseases can cause all proteins to inhibit. Instead of closing around the cell and bumping into each other to carry out vital tasks, these proteins get stuck in chemical traffic jams, creating a type of widespread sluggishness called “proteolethargy.”

Such hibernation occurs when proteins with a sticky building block on their surface interact with harmful byproducts from chronic inflammation and stress, causing the proteins to clump together and crawl to a near stop, researchers report Nov. 27 in Cell.

The result: Cells struggle to function, causing important biological systems to collapse—a hallmark of aging-related diseases.

This molecular barrier may be a “common denominator” that underpins many of life’s diseases, says cell biologist Alessandra Dall’Agnese, of the Whitehead Institute for Biomedical Research in Cambridge, Mass. “It’s a unifying mechanism.”

Nearly half of all proteins in the body carry the sticky residue implicated in protein malfunction, putting at risk of halting countless cellular processes—metabolism, cell repair, immune defense, gene regulation, and more.

Antioxidants and drugs that counteract protein adhesion can partially restore protein mobility, Dall’Agnese and her colleagues point out in the paper. The findings could pave the way for therapies designed to alleviate these molecular barriers and address the root causes of chronic disease.