Long Live Collagen

Increased collagen expression is a common feature of many different pathways to extended longevity in worms.

Mar 1, 2015
Ashley P. Taylor

AGING WORMS: Young (left) and old (right) specimens of the nematode C. elegansCOURTESY OF KEITH BLACKWELL

EDITOR'S CHOICE IN MOLECULAR BIOLOGY

The paper
C.Y. Ewald et al., “Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity,” Nature, doi:10.1038/nature14021, 2014.

The impetus
One of the earliest observations about longevity in the roundworm Caenorhabditis elegans, a choice model organism for aging research, was that the worms live longer when the insulin/insulin-like growth factor 1 pathway is disrupted. This disruption normally sends worms into a hibernation-like state, called dauer, which increases life span by inserting a pause into the life cycle. Keith Blackwell of Boston’s Joslin Diabetes Center and colleagues wondered if blocking the insulin/IGF1 pathway could increase life span even without this hiatus.

The results
To this end, the researchers reduced the insulin/IGF1 pathway at temperatures that block entry into the dauer state, and the worms still lived longer. The team looked for changes in gene expression that accompanied this phenomenon and found the most striking upregulation among collagen genes. Such an uptick in expression was not unique to disabling insulin signaling; Blackwell’s group found that collagens were also boosted in several other interventions that extended life span in C. elegans.

The implications
Collagens are most familiar as the proteins whose age-related dysfunction causes wrinkles. “This paper really suggests that collagens are not just, let’s say, associated with external, . . . cosmetic usefulness, but overall improved health,” says Malene Hansen of La Jolla’s Sanford-Burnham Medical Research Institute. The study also suggests a new role in aging for the extracellular matrix, where collagens are found. “Mechanisms that will extend life [may] act by enhancing the function of the extracellular matrices and specifically of collagens,” says Blackwell.

Remaining wrinkles
Whether collagen decline leads to aging or vice versa is an area for future research. “There’s likely to be sort of a feedback loop” between the two, says Hansen.