New research in simple animals suggests that combining mutants 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.
100% plus 30% equals 500% life extension because of synergies
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.”
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Citation: “Germline Signaling Mediates the Synergistically Prolonged Longevity by Double Mutations in daf-2 and rsks-1 in C. elegans”; Cell Reports.
Highlights
* The daf-2 rsks-1 double mutant shows synergistic lifespan extension in C. elegans
* AMPK mediates positive feedback regulation of DAF-16 in daf-2 rsks-1
* Germline tissue is a key tissue in modulating this synergistic longevity
* Inhibiting rsks-1 in the germline leads to cell-nonautonomous activation of DAF-16
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100% plus 30% equals 500% life extension because of synergies
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.”
Citation: “Germline Signaling Mediates the Synergistically Prolonged Longevity by Double Mutations in daf-2 and rsks-1 in C. elegans”; Cell Reports.
Highlights
* The daf-2 rsks-1 double mutant shows synergistic lifespan extension in C. elegans
* AMPK mediates positive feedback regulation of DAF-16 in daf-2 rsks-1
* Germline tissue is a key tissue in modulating this synergistic longevity
* Inhibiting rsks-1 in the germline leads to cell-nonautonomous activation of DAF-16
Read more »
