As we age, our cells can accumulate damage, partly because our in-built repair mechanisms don’t work as well as they did when we were young. Damaged cells can give off signals that cause problems for surrounding cells, in effect, taking healthy cells down with them. An organ, like the liver, doesn’t work well as a whole if some liver cells are healthy, and some are unhealthy. Scientists call this tissue heterogeneity and it causes problems in how cells signal to each other and work as one cohesive unit.
So it is important to know how the young body recognises and removes damaged cells to keep tissues healthy. Once we know that, we might be able to make sure this process keeps happening as we age. This might, if we’re really lucky, slow down ageing.
Scientists studying the fruit fly have worked out the genes and proteins that tag cells as ‘unhealthy’. They found that flies with higher than normal levels of a single gene called azot can eliminate defective cells more quickly and efficiently than flies with normal azot levels. Super-azot flies live 50-60% longer than normal flies and their tissues, like the brain, stay healthy and young looking for longer. The opposite is also true. Flies with lower than normal azot levels live 50% shorter than normal flies. The wings of azot-deficient flies don’t develop properly and their brains breakdown more quickly than normal flies.
So how does this magical longevity gene work?
Two proteins, called Flower and Sparc (yes fly people call fly genes weird names), work together to mark a cell as ‘healthy’ or ‘unhealthy’. The azot gene is then turned on in unhealthy cells. azot stimulates a process called apoptosis, or programmed cell death, effectively telling the unhealthy cells to commit suicide (cell-icide). If there is not enough Flower or too much Sparc, azot is not turned on and the cell does not die.
When the scientists blocked this process, by removing azot, they found that flies aged faster and didn’t live as long. Also the azot-less were less resistant to tissue damage. When these flies were irradiated with UV light, 99% of them died within six days, compared with only 67% of normal flies. When scientists increased levels of azot in flies, the super-azot flies aged more slowly and lived longer and were more resistant to tissue damage from UV light. The super-azot flies lived even longer (35% longer) when their diets were restricted. Dietary restriction is a well known way to extend the lifespan of flies, worms and even mice. It isn’t yet entirely clear whether this approach also works in monkeys and humans.
It is pretty amazing to think that a single gene can have such a profound effect on ageing. It goes against everything that I believe about ageing. I view ageing as a complex process that can’t be controlled by one gene. Maybe I’m wrong?
It will be interesting to see whether the same process is occurring in humans. Mice also have Flower proteins but as far as I know, no one has looked at whether azot works with Flower in mice the way it does in flies. And no one has looked at this interaction in humans.
The Scientific Paper (free and open access):