Time is not good for us. As we age, condition of our bodies start to decline right to the cellular level. A lot of the age-related gastrointestinal problems can be traced to ageing cells of the intestinal epithelium. But now scientists from the University of Helsinki and Karolinska Institutet found a way to rejuvenate the regenerative potential of an aged intestine.
We stay young as long as our tissues are regenerated. However, they lose this ability with age. And that’s a problem, because in a big part of the world population is ageing rapidly. For example, ageing intestinal epithelium increase the risk of drug intolerance. This means that ageing intestines make dosing of many common medicine challenging. But what can be done? Scientists have just discovered how regenerative capacity of intestinal epithelium declines and found ways to reverse that.
The key is Notum – an enzyme, inhibitor, which inhibits stem cell maintaining signaling. Reducing Notum results in rejuvenation of the regenerative potential of an aged intestine. Targeting Notum could provide a new way to increase the therapeutic window, when medicines are tolerated easier. Scientists are at the beginning of creating of a new drug therapy, which would improve the regeneration potential of the intestinal epithelium, however, lifestyle changes could bring a positive result as well.
Scientists used organoid culture methods and found the culprit – the poor function of tissue repairing stem cells in old intestine was due to aberrant signals from the neighboring cells, known as Paneth cells. Nalle Pentinmikko, one of the authors of the study, said: “Modern techniques allowed us to examine tissue maintenance at a single cell level, and revealed which cell types contribute to the decline in tissue function. We were surprised to find that even young stem cells lost their capacity to renew tissue when placed next to old neighbors”.
So this is how it works. Normally, intestine cells are able to regenerate because of stem cells that rely on activity of Wnt-signaling pathway. Notum enzymatically inactivates Wnt-ligands, which decreases the ability for cells to regenerate. This causes tissues to age. If we inhibit the Notum enzyme, intestine cells are able to rejuvenate. Scientists already confirmed it in experiments with animals.
Population is ageing and scientists are trying to fight it. Holistic view is, of course, appealing, but better results are achieved trying to stop separate processes of ageing. Hopefully, this research will continue to move ahead and intestines will be healthy for longer.
Source: University of Helsinki