Sluggish proteins may underpin 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 may contribute to the development of chronic health issues.

Molecular stress brought on by diabetes, fatty liver disease and other chronic conditions can all cause proteins to put on the brakes. Instead of zipping around the cell and bumping into each other to perform vital tasks, these proteins become ensnared in chemical traffic jams, creating a kind of widespread sluggishness termed “proteolethargy.”

Such lethargy occurs when proteins with a sticky building block on their surface interact with harmful by-products from chronic inflammation and stress, causing the proteins to clump together and crawl to a near standstill, researchers report November 27 in Cell.

The result: Cells struggle to function, triggering the collapse of crucial biological systems — a hallmark feature of aging-related maladies.

This molecular bottleneck may be a “common denominator” underpinning many of life’s ailments, 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 countless cellular processes — metabolism, cell repair, immune defense, gene regulation and more — at risk of grinding to a halt.

Antioxidants and drugs that counteract the stickiness of proteins can partially restore protein mobility, Dall’Agnese and her colleagues note in the paper. The findings could pave the way for therapies designed to ease these molecular roadblocks and tackle the root causes of chronic disease.