Tenfold Healthy Life Extension in Nematodes

I first noted the gene engineering work on nematode worms that led to a tenfold extension of healthy lifespan late last year:

This and similar work forms an impressive set of technology demonstrations - there is no necessarily direct relevance to extending healthy human life span, but it certainly gets people fired up and excited.

Similar work that immediately springs to mind is the recent news of tenfold healthy life extension in yeast and 50% healthy life extension in mice, both also achieved through gene engineering.

More details on the nematode work (in the species C. elegans) are now available for those of us without a journal subscription at the UAMS website:

C. elegans are barely visible to the eye but are helping scientists unravel the causes of aging and understand what determines life span, Reis said. During the past 15 years, more than 80 mutations have been found that extend life in C. elegans, including components of a worm signaling pathway (a set of genes that responds to signals from the environment or within the worm) that is equally related to insulin signaling and insulin-like growth factor (IGF-1) signaling in mammals.

Insulin alerts cells that there are nutrients in the blood ready to be used, whereas IGF-1 stimulates growth. Interfering with insulin signaling results in insulin resistance, a condition that can develop into diabetes. Interfering with IGF-1 signaling produces effects in mammals more akin to those seen in long-lived worms. Mice mildly deficient in IGF-1 receptor are long-lived and appear healthy, Reis said, adding that the longest-lived humans tend to have diminished IGF-1 signaling as well.

“These observations hint that processes discovered in the worm also are relevant to aging in humans," Reis said, "but we shouldn’t expect exact parallels."

Reis' team discovered that a mutant in the insulin/ IGF-1 pathway of C. elegans slows development but ultimately produces adults he described as "super survivors," able to resist levels of toxic chemicals that would kill an ordinary worm. Although the adult lifespan of C. elegans is normally only two to three weeks, half of the mutant worms were still alive after six months, with some surviving to nine months.

"We knew we had found something amazing," said Srinivas Ayyadevara, Ph.D., research assistant professor in the UAMS Donald W. Reynolds Institute on Aging. "These worms continue to look and act like normal worms of one-tenth their age."

For those of you who like to dig deeper, a PDF of the scientific paper is freely available as well.