Wouldn’t it be marvellous if there was a medicine that could rejuvenate and ‘youthify’ both ageing muscles and ageing brains? We don’t have it yet but it may not be too far away either.
Last week, researchers from the Berkeley Stem Cell Center at the University of California, Berkeley presented the findings of their research looking at the potential of single molecule drug to simultaneously ‘perk up’ old stem cells in the brains and the muscles of mice and restore much of their youthful functioning.
They have found that a small molecule – called an ‘Alk5 kinase inhibitor’ – which is already undergoing trials as an anticancer agent, successfully renewed stem cell function in both brain and muscle tissue of the same old mouse, potentially making it stronger and more clever.
It is only a first step toward an actual therapy since there are other biochemical factors involved in adult stem cell activity which need to be addressed. But the researchers are already collaborating on an approach which they hope could safely achieve that in the future.
Here’s how it works:
We know that ageing is, in part, caused by adult stem cells failing to generate replacements for damaged cells and thus repair the body’s tissues. Researchers have shown that certain chemicals around the adult stem cells are the main culprit in this diminished stem cell activity.
So the thinking has been, if it is possible to change the chemical environment around the adult stem cells (make it more like it is in younger stem cells), then the ageing stem cells might be able to get back into business.
Ten years ago, Berkeley researchers demonstrated that infusing old mice with blood from young mice reinvigorated stem cells in the muscle, liver and brain/hippocampus. This showed that it was possible to rejuvenate the chemical environment of the ageing stem cells by introducing ‘fresh, young’ chemicals found in young blood.
They have recently begun a small trial to see if blood plasma from young people can help reverse brain damage in elderly Alzheimer’s patients.
While this is all very positive, the problem is that these sorts of therapies are not easy to deliver and can have dangers associated with them. So the researchers are trying to find a safer and more practical approach to delivering the ‘youthful’ chemicals into the ageing stem cell environment.
A key ingredient
They have identified a chemical called TGF-beta1 that is present in all tissues of the body, including the hippocampus in the brain, but the levels of it tend to increase with age. And the problem is that high levels of TGF-beta1 have been shown to depress stem cell activity.
Enter the small molecule called the Alk5 kinase inhibitor – a chemical known to block and reduce the effect of TGF-beta1. By injecting the Alk5 kinase inhibitor into the blood of the old mice, the researchers were able to reduce TGF-beta1 levels, with the result that stem cells began to act more youthfully, generating new nerve cells.
One of the leaders of the research, Assistant Professor Irina Conboy, said, “The key TGF-beta1 regulatory pathway became reset to its young signalling levels, which also reduced tissue inflammation, hence promoting a more favourable environment for stem cell signalling.
“You can simultaneously improve tissue repair and maintenance repair in completely different organs, muscle and brain,” she said in a University media statement.
If that doesn’t quite paint the picture for you, she also said the Alk5 kinase inhibitor, already undergoing trials as an anticancer agent, “successfully renewed stem cell function in both brain and muscle tissue of the same old animal, potentially making it stronger and more clever.”
That’s what we like to hear!
Read more about this research at the newscentre on the UC Berkeley’s website by clicking on the link.
