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Researchers at the University of Helsinki have discovered how the regenerative capacity of the intestinal epithelium decreases with age. Targeting an enzyme that inhibits the maintenance of stem cell signaling rejuvenates the regenerative potential of an older intestine. This discovery could pave the way for reducing age-related gastrointestinal problems, reducing the side effects of cancer treatments, and reducing health care costs in the aging society by promoting healing.
"This study highlights the importance of cellular interactions: changes in a cell have resulted in the secretion of an aging factor that can be targeted with drugs, providing many attractive points for interventions," says lead researcher Pekka Katajisto, badociate professor at the University of Helsinki. and Karolinska Institutet.
The reduction of age-induced tissue turnover makes it difficult to administer many common medications. Targeting an inhibitor called Notum could be a new way to increase the therapeutic window and promote recovery in aging societies. The researchers believe that in addition to direct targeting of Notum, lifestyle factors, such as diet, can also reduce Notum and improve tissue renewal and repair.
Using organo-culture methods, the researchers realized that the malfunction of the stem cells repairing the tissues in the old intestine was due to aberrant signals from neighboring cells, called Paneth cells.
"Modern techniques have allowed us to examine the maintenance of tissues at the level of a cell and to reveal what types of cells contribute to the decline of tissue function." We were surprised to find that even the cells Young strains lost their ability to renew the tissues when they were placed next to old neighbors. ", says lead author, PhD candidate Nalle Pentinmikko of the University of Helsinki.
The intestinal epithelium is normally renewed by stem cells that depend on the activity of the Wnt signaling pathway. The surrounding cells produce molecules that activate this pathway. The study shows that, during aging, Paneth cells begin to express a secreted Wnt inhibitor called Notum. Notum enzymatically inactivates Wnt ligands in the stem cell niche, which decreases the regenerative potential of intestinal stem cells. However, pharmacological inhibition of Notum rejuvenated stem cell activity and recovery of older animals after treatment with a chemotherapeutic drug commonly used with serious side effects in the intestine.
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