Scientists have identified 30 genes linked to physical ageing – one of which may possibly be influenced to extend healthy lifespan in humans – after analysing a ‘haystack’ of 40,000 genes from three different organisms.
The researchers from ETH Zurich in Switzerland and the Jena University Hospital in Germany examined around 40,000 genes in the nematode caenorhabditis elegans, zebra fish and mice.
The scientists wanted to determine which genes are regulated in an identical manner in all three organisms in each comparable ageing stage – young, mature and old.
As a measure of gene activity, the researchers measured the amount of messenger RNA (mRNA) molecules found in the cells of these animals.
mRNA is the transcript of a gene and the blueprint of a protein. When there are many copies of an mRNA of a specific gene, it is very active; the gene is upregulated.
Fewer mRNA copies, to the contrary, are regarded as a sign of low activity, said coordinating author Michael Ristow, Professor of Energy Metabolism at ETH Zurich.
Out of this volume of information, the researchers used statistical models to establish an intersection of genes that were regulated in the same manner in the worms, fish and mice.
This showed that the three organisms have only 30 genes in common that significantly influence the ageing process.
By conducting experiments in which the mRNA of the corresponding genes were selectively blocked, the researchers pinpointed their effect on the ageing process in nematodes.
With a dozen of these genes, blocking them extended the lifespan by at least five per cent.
One of these genes proved to be particularly influential: the bcat-1 gene.
“When we blocked the effect of this gene, it significantly extended the mean lifespan of the nematode by up to 25 percent,” said Ristow.
When the researchers inhibited the gene activity of bcat-1, the branched-chain amino acids accumulated in the tissue, triggering a molecular signalling cascade that increased longevity in the nematodes.
Moreover, the timespan during which the worms remained healthy was extended. As a measure of vitality, the researchers measured the accumulation of ageing pigments, the speed at which the creatures moved, and how often the nematodes successfully reproduced.
All of these parameters improved when the scientists inhibited the activity of the bcat-1 gene.
The scientists also achieved a life-extending effect when they mixed the three branched-chain amino acids into the nematodes’ food.
However, the effect was generally less pronounced because the bcat-1 gene was still active, which meant that the amino acids continued to be degraded and their life-extending effects could not develop as effectively.
Ristow has no doubt that the same mechanism occurs in humans.