Synergy Between Mutations in Insulin Signaling and TOR Pathways Extends Life Fivefold in Nematodes
Most interventions that increase longevity in short-lived laboratory species, such as the nematodes used here, are just different ways of influencing the same underlying stress response mechanisms. Thus they don't tend to synergize well with one another. There are exceptions, however, and here researchers demonstrate a strong synergy between mutations in insulin and TOR signaling. It is worth noting that the fivefold life extension achieved here is only half of the present record for nematodes. Very short-lived species like this one exhibit great plasticity of life span in response to interventions, far greater than is the case for mammals, particularly long-lived mammalian species such as our own. We should not expect enormous gains to result from the same approach in humans, even given that the underlying mechanisms of insulin and TOR signaling are surprisingly similar in nematodes and mammals.
Researchers have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research. The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.
Because these pathways are "conserved," meaning that they have been passed down to humans through evolution, they have been the subject of intensive research. A number of drugs that extend healthy lifespan by altering these pathways are now under development. The discovery of the synergistic effect opens the door to even more effective anti-aging therapies.
The new research uses a double mutant in which the insulin signaling (IIS) and TOR pathways have been genetically altered. Because alteration of the IIS pathways yields a 100 percent increase in lifespan and alteration of the TOR pathway yields a 30 percent increase, the double mutant would be expected to live 130 percent longer. But instead, its lifespan was amplified by 500 percent.