Old age is a killer and for a very long time now scientist have known that incidence rates of deadliest chronic diseases such as cancer, diabetes or dementia, increase dramatically as we age. But how do we slow, stop or even reverse these underlying biological mechanisms that drive age-related diseases?
English researchers believe that they’ve discovered a genetic switch that can potentially reset the biological clock in old cells, causing them to look and behave just like spry younger cells. Published in the journal BMC Cell Biology, the discovery was focused on a class of genes called splicing factors that play a critical role in translating genetic information into proteins within a cell.
Lorna Harries is professor of molecular genetics at the University of Exeter and the lead author of the paper. She explains that the job of splicing factors is to cut up sequences of messenger RNA and assemble the specific proteins that cells need to function properly, which includes proteins that help cells respond to stressors from the environment such as infection or damage from free radicals.
“As you get older, your ability to react to the environment decreases,” said professor Harries. “Those splicing factors are some of the main things that help your cells adapt. You could essentially change the gene’s output according to the environment by taking one gene and making a lot of different proteins from it.”
Previous research has shown that these splicing factors become less active as we age, which leaves cells more vulnerable to the outside threats. However it was unclear to Harries if lower levels of splicing factors were one of the causes of age-related decline or just another side effect.
Harries started working with a culture of senescent human cells in order to figure it out. Senescent cells are the ones that have reached their highest limit of cell divisions and then eventually gone inactive. The immune system in a younger healthier body targets these senescent cells and destroys them. So as we reach a certain age and our immune system weakens, more and more of these senescent cells build up in the human body. This procces has been linked with decreased longevity.
Professor Harries and her colleagues from the University of Exeter wanted to see what would happen if they boost the levels of splicing factors in a senescent cell to those of a young, active cell. In order to do that, they synthesized novel versions of a compound called resveratrol, which naturally can be found in chocolate, blueberries, or red wine. This compound gave promising results in previous research for altering the expression of splicing factors.
Harries was amazed by the results that showed all of the splicing factors basically resetting and then returning more or less to the levels that can be seen in young cells.
What was even more incredible, was the fact that the old, senescent cells treated with resveratrol were hard to distinguish compared with the young cells. These “old” cells stared dividing again and their telomeres, which are the caps on the ends of chromosomes that shrink with old age, grew longer.
„When my post-doc brought me pictures of the sells, I didn’t believe it. I said ‘No, you must have the wrong ones, these are the young cells’” said Harries. They had to redo the experiment in order to be sure that it’s not a mistake.
However, this does not mean that the key of a longer, healthier life lies in a box of chocolates washed with a bottle of cabernet, because the naturally occurring form of resveratrol isn’t very bioavailable. This means that very little of the compound actually makes it into your cells and also the synthetic molecules made in the lab performed much better.
The biggest breakthrough of this research is that splicing factors clearly play an active role in the breakdown of the body as we age.
“Those changes that are noticeable in splicing factors are causal,” said Harries. “They’re driving aging; they’re not just an effect of it, because you can reverse the effects of aging if you reset them.”
Harries, like many other researchers before her, is quick to distance her discovery from anything close to a “fountain of youth.” She set up a goal not to increase human lifespan, but to improve “health span”, or the number of years that people can live free of chronic, debilitating diseases associated with old age. A longer health span not only improves people’s quality of life, but it also lowers the cost of healthcare.
This new discovery is the latest addition to a growing scientific understanding of the underlying mechanisms of aging. When these discoveries are taken together, it’s fair to ask whether we’re fast approaching a time when the weaknesses and decline associated with old age are no longer a given.
“That’s what we’re hoping for,” said Harries. “We’re not there yet, and most probably we’re not going to be there in the next 10 or 20 years but the important thing is understanding the basic mechanics of this. It’s absolutely key. I think we’re starting to get to a position now where we’re beginning to uncover those nuts and bolts. And by doing that, we can work out some ways to tweak them.”