JAN 12, 2020

Changing Two Cellular Pathways Extends Lifespan Significantly

WRITTEN BY: Carmen Leitch

Caenorhabditis elegans is a small worm that is a popular research model; it has many genes in common with humans, there are genetic engineering tools that apply to it, it's easy and inexpensive to raise and develops rapidly. Scientists using this model have now found chemical pathways in this organism's cells that can extend the life of this short-lived worm by five times. If a human lived that much longer, they'd be as many as 500 years old.

This work, which was published in Cell Reports, focused on pathways that are also found in humans and have been studied extensively. There are already drugs in development that aim to extend lifespan, and the more we learn about the mechanisms underlying the aging process, the more likely it becomes that a drug to combat aging will be created.

The researchers used worms that had been genetically engineered. The insulin signaling pathway and target of rapamycin (TOR) were altered in the animals and these changes resulted in a 100 percent and 30 percent increase in lifespan, respectively. When both pathways were altered at the same time, lifespan increased by a whopping 500 percent.

"Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn't been clear how these pathways interact," noted Hermann Haller, M.D., president of the MDI Biological Laboratory. "By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population."

"The synergistic extension is really wild," said study author Jarod A. Rollins, Ph.D. "The effect isn't one plus one equals two, it's one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways."

An anti-aging treatment might involve a combination therapy that uses different drugs to act in different ways, just like combination therapies that treat cancer or HIV, noted study author Pankaj Kapahi, Ph.D., of the Buck Institute.

These pathways are complex, with many molecular players, and this research may also help explain why no single longevity gene has been found in people that live healthy lives well into old age.

Rollins is featured in the video above discussing the genetic basis of aging in humans.


Sources: Phys.org via Mount Desert Island Biological Laboratory, Cell Reports