Breakthrough study finds that aging naturally protects against cancer

Most people assume that growing older only raises cancer risk. That idea feels natural because most diagnoses occur after 60. But when you study population data closely, the pattern becomes more complicated. Cancer rates climb through midlife, level off later and then decline in very old age. For years, that curve has confused scientists.

A new study from researchers at Stanford University helps explain why the oldest individuals seem protected. The findings overturn common beliefs about cancer and age and offer a more hopeful picture of how aging shapes the body’s ability to resist tumors.

Researchers created a mouse model that could form lung tumors when exposed to a specific genetic trigger. Young mice were four to six months old. Old mice were 20 to 21 months old. That age range reflects the point in life when many signs of aging appear in mouse tissues.

After scientists activated a cancer-driving KRAS mutation, they waited fifteen weeks. The results were hard to ignore. Older mice developed about one third as much tumor growth as younger ones. Their lungs weighed less, and fluorescent imaging showed far fewer tumors. The difference was not caused by poor viral delivery in older lungs; both age groups were infected at similar rates.

“It’s a striking finding,” said Monte Winslow, an associate professor of genetics and pathology. “We would expect that older animals would get more and worse cancers, but that’s not at all what the study found.”

The results matched a pattern seen in people over 85, whose cancer rates fall rather than rise. For Winslow and his team, this pattern suggested something deeper than missed diagnoses or shifts in healthcare behavior. Instead, aging itself seemed to create conditions that suppress tumor growth.

To measure how age shapes the earliest steps of cancer, the researchers used viral barcodes. Each barcode marked an individual tumor. That allowed them to count how many tumors appeared and how large each one grew.

Again, the results pointed in the same direction. Older mice formed fewer tumors, and the tumors that did form stayed much smaller. The reduction held true in males and females. Age weakened both tumor initiation and growth.

“Aging is a systemic change to your body, but most cancer studies in mice are conducted on younger animals,” said former graduate student and study lead author Emily Shuldiner. “When we introduced the same lung cancer-causing mutations in young and old mice, the young mice develop more, faster growing tumors.”

Her work, published in Nature Aging, shows that aging does not simply push tissues toward cancer. Instead, older tissues can resist tumor development in ways younger tissues cannot.

Cancer begins when mutations push cells to divide uncontrollably. Many cancers progress only after tumor suppressor genes lose their protective function. To understand how age changes these genes’ influence, the team used CRISPR gene editing to inactivate 25 tumor suppressors one by one.

Even here, age played a major role. Most tumor suppressor losses had much weaker effects in older mice. Tumors grew, but the boost provided by those mutations was far greater in younger animals.

One mutation stood out. Inactivating the tumor suppressor PTEN had a powerful effect in young lungs but a far smaller effect in old ones. PTEN normally restrains a growth pathway called PI3K-AKT. When PTEN was removed in young mice, tumors soared. In old mice, the same mutation mattered far less.

“PTEN inactivation stood out as having a much stronger effect in young mice,” Shuldiner said. “It suggests that the effect of any given mutation, or the efficacy of cancer therapies targeted at specific mutations, might be different in young versus old people.”

To see how age changes the inner workings of cancer cells, the team analyzed around 180,000 single cells from tumor-bearing lungs. They discovered that cancer cells in older lungs still carried strong signs of aging even though tumors divide quickly.

“We found that patterns known to be associated with aging were still present in the cancer cells from old mice,” Shuldiner said. “This was not an obvious finding because cancer cells are rapidly dividing.”

The picture changed when PTEN was removed. Cancer cells in old mice lost many of their aging fingerprints and began to look more like cancer cells from young animals. These age-erasing changes spread to surrounding immune and stromal cells, suggesting that PTEN loss resets whole neighborhoods of tissue.

The study supports a new view of cancer and aging. Throughout life, mutations accumulate that raise cancer risk. At the same time, tissues gradually adopt features that make it harder for tumors to begin or grow. Those changes strengthen late in life and may help explain why cancer rates decline near the end of the lifespan.

“The implications of this story could be huge,” said Dmitri Petrov, professor of biology. “Maybe aging has a beneficial side to it that we could harness for better therapies.”

Winslow agrees. “We develop these animal models of cancer with an eye to developing new treatments for patients,” he said. “But for this to work, the models have to be correct. And this study suggests that models using young animals may not be accurately reflecting important aging-related changes.”

Research findings are available online in the journal Nature Aging.

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