The ‘weakest link’ in the aging proteome

Proteins are the chief actors in cells, carrying out the duties specified by information encoded in our genes. Most proteins live only two days or less, ensuring that those damaged by inevitable chemical modifications are replaced with new functional copies.

In a new study published August 29 in Cell, a team led by researchers at the Salk Institute for Biological Studies and The Scripps Research Institute (TSRI) have now identified a small subset of proteins in the brain that persist for longer, even more than a year, without being replaced.

These long-lived proteins have lifespans significantly longer than the typical protein, and their identification may be relevant to understanding the molecular basis of aging.

"Protein longevity can be a major contributor to cellular aging," says Martin Hetzer, a professor in Salk's Molecular and Cell Biology Laboratory and holder of the Jesse and Caryl Philips Foundation Chair, who was a senior author of the study with TSRI Professor John Yates. "Simply identifying all long-lived proteins allows us to focus our studies on these specific proteins, which may be the weakest link in the aging proteome."

The study provides the first comprehensive and unbiased identification of the long-lived proteome, the entire set of proteins expressed by a genome under a given set of environmental conditions. In a study published in Science last year, Hetzer and his colleagues identified long-lived proteins in one sub-cellular location, namely the nucleus.