What are the limits to longevity? Recent research in simple animals demonstrates that combining mutations can lead to radical lifespan extension. Scientists at the Buck Institute combined mutations in two pathways well-known for lifespan extension and report a synergistic five-fold extension of longevity in the nematode C. elegans. The research, done at the Buck Institute and published online in Cell Reports on December 12, 2013, introduces the possibility of combination therapy for aging and the maladies associated with it.
The mutations inhibited key molecules involved in insulin signaling (IIS) and the nutrient signaling pathway Target of Rapamycin (TOR). Lead scientist and Buck faculty Pankaj Kapahi, PhD, said single mutations in TOR (in this case RSKS-1) usually result in a 30 percent lifespan extension, while mutations in IIS (Daf-2) often result in a doubling of lifespan in the worms — added together they would be expected to extend longevity by 130 percent. “Instead, what we have here is a synergistic five-fold increase in lifespan,” Kapahi said. “The two mutations set off a positive feedback loop in specific tissues that amplified lifespan. Basically these worms lived to the human equivalent of 400 to 500 years.”
Kapahi said the research points to the possibility of using combination therapies for aging, similar to what is done for cancer and HIV. “In the early years, cancer researchers focused on mutations in single genes, but then it became apparent that different mutations in a class of genes were driving the disease process,” he said. “The same thing is likely happening in aging.” Kapahi said this research could help explain why scientists are having a difficult time identifying single genes responsible for the long lives experienced by human centenarians. “It’s quite probable that interactions between genes are critical in those fortunate enough to live very long, healthy lives.”
Metformin is gaining increasing attention from researchers as it has been indicated as a geroprotector, i.e. a drug able to prolong lifespan.