Scientists find genetic secret of longer life

A gene that can lengthen an organism’s lifespan has been discovered for the first time in experiments on yeast, promising new insights into human ageing.Research in the US revealed that yeast strains with versions of a gene known as PNC1 live for up to 70 per cent longer than those with a different genetic configuration.

The findings, from a team at Harvard Medical School, suggest that PNC1 is the first genetic regulator of lifespan discovered. As similar genes probably exist in humans, scientists hope that it may one day be possible to manipulate or simulate them to extend life and protect health against the ravages of old age.

The PNC1 gene has its effect because it responds to environmental factors that are known to influence lifespan in many organisms.

Researchers have known for several years that restricting the food intake of yeast, fruit flies, worms and rats so that many fewer calories are consumed can significantly lengthen these organisms’ lives, and PNC1 appears to play a vital part in this process in yeast.

The gene is required if yeast is to derive any benefit from calorific restriction, according to the study led by David Sinclair, of Harvard Medical School. Strains with five copies of the gene generally live 70 per cent longer than wild strains, which have only one copy — the longest lifespan extension seen in yeast.

The results, details of which are published today in the journal Nature, show that lifespan is not determined solely by accumulated wear and tear on the body, or the rate of metabolism, as some researchers have suggested. Genetic factors are intimately involved as well, and these may explain whether and how environmental factors affect longevity.

“In contrast to the current model, we show that the lifespan extension from calorie restriction is the result of an active cellular defence involving the up-regulation of a single gene,” Dr Sinclair said.

Levels of the protein produced by PNC1 are also raised when yeast is exposed to high temperatures — another type of stressful environment that is known to prolong the organsim’s lifespan.

The research team, who conducted their experiments using a strain of yeast known as Saccharomyces cerevisiae, are now investigating the human genome for genes that may play a similar role in longevity to PNC1. The picture, however, is almost certain to be far more complicated in humans, Dr Sinclair said.

The PNC1 protein has its effect in yeast by affecting levels of Sir2, another protein that helps cells to survive by keeping their DNA stable. PNC1 converts a vitamin called nicotinamide, which inhibits Sir2 production, into nicotinic acid, which does not have the same harmful effect and allows Sir2 levels to rise.

While yeast has only one Sir protein, Sir 2, humans have seven, meaning that the genetic levers that influence human ageing will be harder to understand and manipulate