Dietary restriction (eating less calories while still eating enough nutrients) is a powerful anti-ageing treatment. Animals from yeast all the way up to monkeys live longer when they eat less calories. Since no one wants to diet, and everyone wants to live longer, scientists have been trying to find drugs that mimic the anti-ageing effects of calorie restriction.
When we eat less, there is less energy available to our cells. Therefore, the body has to break down molecules in our cells to use them for energy. This process is called autophagy. The molecule AMPK senses how much energy is available inside each cell. If energy levels are low, AMPK stops the cell from making new proteins and kickstarts autophagy. This not only provides energy for the cell to survive, but it is also a sort of spring cleaning of the cell. Organs age better when autophagy is induced.
When AMPK levels are increased in worms or flies, they live longer. The question is whether AMPK levels need to be increased in the whole body to have an anti-ageing effect, or whether more AMPK in just one organ, like the brain or the intestine is enough for a longer life.
A recent study found that activating AMPK in neurons causes autophagy in the brain, intestine and skeletal muscle, and this slows ageing in the whole body. Flies with more brain-AMPK eat and exercise the same amount as control flies, but they live longer. This sounds a little like the holy grail of ageing research. As flies age, their muscles get weaker, just like in humans. Activating AMPK in fly neurons delayed this age-related muscular dysfunction.
The same result was seen when AMPK was up-regulated only in the flies’ intestines. These flies lived longer, had more autophagy in their brains, intestines and muscles and had delayed intestinal dysfunction with age.
AMPK works, in part, by activating the protein Atg1 (Autophagy-specific gene 1). If scientists inhibited Atg1 in the fly brains, then over-expressing AMPK no longer extended their lifespan. AMPK required Atg1 to work. So next, the scientists asked whether activating Atg1 alone could have the same effects as up-regulated AMPK. And it did. Flies with more Atg1 in their neurons also lived longer thanks to increased autophagy in their brain and intestine.
Increasing AMPK or Atg1 in fly brain or intestine affected many tissues in the body the same way that calorie restriction does. It reduced the amount of insulin-like peptides and increased the amount of 4EBP, a protein that can regulate the rate at which many other proteins are made in the cell.
The next logical step is to to do the same experiment in mammals.
The Scientific Paper: