Scientists have discovered a hidden aging program in the intestines that increases the risk of cancer

A new study published in Aging nature It shows that these changes follow a clear pattern rather than appearing randomly. The international research team was headed by Professor Francesco Neri from the University of Turin in Italy. Scientists have identified a process they call age-related drift and colon cancer, a gradual shift in epigenetic marks that become stronger with age. “We are observing a genetic pattern that becomes increasingly pronounced with age,” says Professor Neri, who was a former group leader at the Leibniz Institute for Aging – Fritz Lippmann Institute in Jena.

Aging patterns associated with cancer risk

The genes most affected by this drift are those that help maintain normal tissue homeostasis. Many of them are involved in regeneration of the intestinal lining through the Wnt signaling pathway. When these genes are altered, the intestine’s ability to repair itself begins to be impaired.

The researchers found that the same pattern of drift appeared not only in senescent intestinal tissue, but also in almost all of the colon cancer samples they analysed. This overlap suggests that senescent stem cells may create conditions that make cancer more likely to develop.

A mixture of aging within the gut

One surprising finding is that aging does not affect the intestines equally. The intestine is made up of small structures called crypts, each made up of a single stem cell. If that stem cell develops genetic changes, every cell within the crypt inherits them.

Dr. Anna Krypelova explains how this process works. “Over time, more and more regions with an older epigenetic profile develop in tissues. Through the natural process of crypt partitioning, these regions continually expand and can continue to grow over many years.”

As a result, the intestines of older people become a mixture of younger and older crypts. Some areas remain relatively healthy, while other areas are more likely to produce damaged cells, which increases the chances of cancer growing.

Iron loss disrupts DNA repair

The researchers also revealed why this epigenetic drift occurs. As intestinal cells age, they take in less iron while excreting more of it. This reduces the amount of iron(II) available in the cell nucleus. Iron(II) is essential for the proper function of TET (ten-eleven translocation) enzymes, which normally help remove excess DNA methylation.

When iron levels decrease, these enzymes no longer work efficiently. As a result, excess DNA methylation remains in place rather than being disassembled.

“When there is not enough iron in the cells, the wrong marks remain on the DNA,” says Dr. Anna Krepelova. “The cells lose their ability to remove these marks.” As TET activity decreases, DNA methylations accumulate, and key genes are turned off, “silent.” This chain reaction accelerates epigenetic drift.

Inflammation accelerates the aging process

Age-related intestinal inflammation exacerbates the problem. The team showed that even mild inflammatory signals can disrupt intracellular iron homeostasis and put additional stress on metabolism. At the same time, Wnt signaling is weakened, reducing the ability of stem cells to remain active and healthy.

Iron imbalance, inflammation, and decreased Wnt signaling act together as an accelerator of epigenetic drift. For this reason, aging in the gut may start earlier and progress faster than scientists previously thought.

Can intestinal aging be slowed?

Despite the complexity of these processes, the results offer some hope. In laboratory experiments using organoid cultures, miniature intestinal models grown from stem cells, researchers were able to slow or partially reverse epigenetic drift. They achieve this by restoring iron uptake or by directly enhancing Wnt signaling.

Both approaches reactivated TET enzymes and allowed cells to begin removing excess DNA methylation again. “This means that epigenetic aging does not have to be a fixed end state,” says Dr. Anna Krypelova. “For the first time, we see that it is possible to modify aging factors located deep within the molecular core of the cell.”