‘In principle, if you understand the mechanisms of keeping things repaired, you could keep things going indefinitely,’ says Cynthia Kenyon, biochemist at the University of California at San Francisco. In her lab she has increased the life span of tiny worms called Caenorhabditis elegans up to six times their normal lifespan by suppressing a single gene. This regulator gene, named daf-2, in combination with other genes, appears to control an entire cluster of genes that direct aging not only in worms, but in similar genetic pathways in flies, mice and, possibly humans. This is the equivalent of people living for 400 years, and the good news is that the worms stay young for most of their extended lifespans.
Diet it seems is a major contributory factor.An experiment with the worms proves that sugar turns on a genetic sequence that increases the amount of insulin produced by an organism, which in turn causes the body to demand more sugar. This increases damage to cells in the body, speeding up the slow degradation of cells that contribute to aging. Red wine and green tea have been shown to help repair cells and contribute to an increased lifespan.
The most significant finding is that the worms remained vigorous till until the very end of their extended lives. In human terms it would mean that a person would remain young for decades, growing old very slowly. It also suggests a radical new method for treating maladies of aging such as Alzheimer’s, Huntington’s and some cancers, which might be put off or eliminated if youth is extended. ‘Age is the single largest risk factor for an enormous number of diseases,’ says Kenyon. ‘So if you can essentially postpone aging, then you can have beneficial effects on a whole wide range of disease.’
When asked whether it was possible to be immortal Kenyon says ‘I think it might be possible. I’ll tell you why. You can think about the life span of a cell being the integral of two vectors in a sense, the force of destruction and the force of prevention, maintenance and repair. In most animals the force of destruction has still got the edge. But why not bump up the genes just a little bit, the maintenance genes. All you have to do is have the maintenance level a little higher. It doesn’t have to be much higher. It just has to be a little higher, so that it counterbalances the force of destruction. And don’t forget, the germ lineage is immortal. So it’s possible at least in principle.’
The daf-2 gene encodes an insulin-like receptor in the worm C. elegans. Mutations in daf-2 have been shown by Cynthia Kenyon to double the lifespan of the worms. The gene is known to regulate reproductive development, ageing, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and also resistance to bacterial pathogens.
DAF-2 is the only insulin/IGF-1 like receptor in the worm. Insulin/IGF-1-like signaling is conserved from worms to humans. DAF-2 acts to negatively regulate the forkhead transcription factor DAF-16 through a phosphorylation cascade. Genetic analysis reveals that DAF-16 is required for daf-2-dependent lifespan extension and dauer formation. When not phosphorylated, DAF-16 is active and present in the nucleus.