Ageing is a state of mind

Scientists have found one gene that can change brain signalling and slow ageing.

ageing manEven though we are very different from worms, fish and mice, we have a lot of the same genes as these animals. This is because we are actually very similar on a basic cellular level. That’s why scientists use animals as genetic models for humans.

A group of scientists recently searched for genes that might control ageing in humans by measuring gene expression changes in ageing worms, fish and mice. They found 29 human genes that were either turned on or off with age in all three animal species.

The scientists then turned each of these 29 genes off in worms to see whether this could slow ageing in worms. They used worms for this experiment because it is easy to turn off genes in worms by adding drugs to their food. These drugs, called interfering-RNAs, bind to a particular gene and stop it from being expressed.

The scientists found that turning off a single gene called bcat-1 (branched-chain amino acid transferase-1) caused worms to live 25% longer. The worms also stayed healthier and more active for longer.

Ageing affects how our genes are expressed. Turning off the bcat-1 gene and normal ageing in worms cause similar changes in 3000 genes, including genes involved in important signalling in the brain, such as TGF-beta.

So how might the bcat-1 gene control ageing? Bcat-1 makes an enzyme that is needed to break down branched chain amino acids (BCAAs). The BCAAs leucine, isoleucine and valine are three of the nine essential amino acids that humans must eat to survive.

When bcat-1 is inhibited in worms, BCAAs accumulate. The long-lived bcat-1-deficient worms had increased level of amino acids in their brains. This activated a molecule called mTOR in the worms’ brain cells. The treated worms didn’t live any longer than untreated worms if mTOR was turned off which means that bcat-1 cannot slow ageing without mTOR. This is a really interesting result because many previous studies have shown that inhibiting mTOR with the drug rapamycin can increase the lifespan of many different animals. Perhaps these conflicting results are because this study found mTOR to be up in the brain of the worms whereas in previous studies mTOR was inhibited in all parts of the body.

Worms fed leucine, isoleucine or valine also lived longer than worms not given these supplements. So it was not necessary to manipulate the bcat-1 gene to increase lifespan. It was enough to give BCAA supplements in the worm food.

BCAAs are found in high protein foods such as meat, eggs, beans and nuts. BCAA supplements have also been used to improve appetite in burn victims and patients with ALS, liver disease, kidney disease and cancer. However more research needs to be done before we all rush out to buy BCAA supplements. We still don’t know what dose of BCAA is safe in humans. Too much could be dangerous as a fatal disease caused Maple syrup urine disease is caused by excessively high BCAA levels due to mutations in enzymes that break down these amino acids.

The Scientific Paper (free and open access): 

Mansfeld et al. Branched-chain amino acid catabolism is a conserved regulator of physiological ageing. Nature Communications. 2015.

 

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