Extreme Old Age Appears to Suppress Lung Cancer Growth in Mice, Offering New Clues About Cancer and Aging

A new study led by researchers at Stanford University has uncovered a surprising and genuinely intriguing pattern: very old mice develop far fewer and smaller lung tumors than younger mice, even when both groups carry the same cancer-causing genetic mutations. This finding challenges one of the most familiar assumptions in cancer biology—that cancer risk simply increases as we age—and instead suggests that extreme aging itself may involve built-in mechanisms that limit how tumors form and grow.

The research, published in Nature Aging, examined how lung cancer progresses in young mice between four and six months old and in older mice aged 20 to 21 months, which is near the maximum lifespan of a laboratory mouse. The results were striking. After inducing identical cancer-driving mutations in both groups and waiting 15 weeks, the older mice showed roughly three times less tumor mass than the younger animals. They also developed fewer tumors overall, and the tumors that did appear were significantly smaller.

The younger mice consistently displayed more aggressive and fast-growing cancers across every measurable category. This outcome ran completely counter to what many scientists would have expected. The long-standing belief has been that as organisms age, they accumulate harmful DNA mutations, suffer declines in cellular repair systems, and experience increased genomic instability—all of which should lead to a higher likelihood of cancer. Yet the study’s findings point to the possibility that, at very advanced ages, biological changes associated with aging may start working in the opposite direction.

Understanding Why Cancer Doesn’t Keep Rising Forever

In humans, cancer incidence rises sharply from midlife onward and typically peaks between ages 70 and 80. However, after age 85, the population-level risk levels off or even declines. There has been ongoing debate over whether this drop reflects biological changes or simply lower screening rates in the oldest age groups. These new mouse findings strongly support the idea that biology plays a major role—to the point that aging might naturally suppress tumor development under some conditions.

Aging brings widespread molecular changes to the body. DNA methylation patterns shift. Genomes become more structurally unstable. Various segments of DNA may duplicate and reintegrate in unpredictable ways. Mitochondrial DNA can move into new regions of the genome. Most discussions of these changes focus on how they can increase cancer risk. But this study suggests that some age-related alterations may hamper cancer instead of encouraging it. For example, age-associated changes might reduce the capacity of certain cells to divide rapidly—a key requirement for tumor growth.

Waiting for the Mice to Grow Old

One of the reasons this topic has not been studied deeply before is practical: cancer research usually relies on young mice because they are cheaper, healthier, easier to maintain, and faster to work with. In this experiment, the researchers had to wait nearly two years—the natural lifespan of mice—to obtain enough very old animals for the test.

The mice used in the study were genetically engineered so that their lung tumors would glow under imaging, allowing the team to accurately measure tumor size and number. After inhaling a gene-delivery system that activates oncogenic KRAS, tumors began forming. When the researchers later compared lung weights, tumor counts, and fluorescence imaging, the differences between young and old animals were undeniable. Every metric showed weaker cancer development in the older group.

Testing Tumor Suppressor Genes

The study went further by evaluating the influence of disabling 25 different tumor-suppressor genes before inducing cancer. Tumor suppressors are genes that normally help prevent cancer formation by blocking harmful cellular growth.

For most of the genes examined, the absence of the tumor suppressor increased cancer formation in both young and old mice—but the effect was always stronger in the younger group. Among all the genes tested, the tumor suppressor PTEN produced the most dramatic difference. When PTEN was inactivated, tumor growth surged especially aggressively in young mice, while old mice still showed a smaller, more muted cancer response.

This suggests that the impact of cancer-related mutations depends greatly on age, and that older tissues may resist some of the worst effects of such mutations. This also means that age could influence how effective certain cancer drugs are, since many therapies target specific mutations or pathways that might behave differently in older bodies.

Aging Signatures Persist Even Inside Cancer Cells

The researchers also investigated how gene expression patterns differed between cancer cells taken from old and young mice. Surprisingly, cancer cells from the older mice still displayed clear signatures of aging. This was unexpected because cancer cells divide rapidly, and rapid cell division often erases many age-related molecular patterns. Yet these “aging signatures” persisted, indicating that even transformed cancer cells retain aspects of the aged environment they came from.

When PTEN was disabled, however, those aging signatures largely disappeared in the older mice’s cancer cells, making them resemble the more youthful, aggressive cancer cells from younger animals. This supports the idea that certain mutations can override protective age-related changes.

Why These Results Matter

This study importantly shows that extreme aging can suppress tumor initiation and growth, and that age changes how tumor suppressor genes function. It highlights that cancer models based solely on young animals may miss critical factors, especially since most human cancer patients are older. If we want accurate models for designing therapies—particularly therapies intended for seniors—we need models that reflect the biological realities of aging.

The findings also open new avenues for therapy development. If scientists can identify precisely which age-related changes inhibit tumor formation, they might be able to mimic those changes in younger individuals or design drugs that artificially trigger similar protective states.

Additional Context: How Aging Affects Cancer Risk

Beyond this specific experiment, aging influences cancer in many complex ways:

Stem-cell exhaustion reduces the number of cells capable of dividing frequently—possibly decreasing the chance of a cell turning cancerous.
Cellular senescence, where cells permanently stop dividing, prevents tumor growth but can contribute to inflammation.
Weakened immune systems in old age may struggle to fight existing cancers but may also respond differently to early tumor cells.
Metabolic shifts, such as reduced nutrient availability, might slow tumor growth.

Cancer itself is not a single disease, and aging affects each tissue differently. While this study focused on lung cancer driven by one specific mutation (KRAS), other tissues and mutations may behave in entirely different ways. Still, this research adds important evidence that the story of cancer and aging is much more complex than “older equals more cancer.”

The Big Picture

The most intriguing message from this research is that aging is not a simple accumulation of problems. Some of its changes might act as natural brakes on tumor formation. Understanding those brakes could be a key step in developing more effective, age-appropriate cancer treatments. It also raises an important question: could we eventually develop therapies that harness or replicate these protective aging-related shifts?

For now, the findings underscore just how important it is to study cancer across the full lifespan—not just in convenient young models. Cancer biology changes with age, and future research and therapy development must take that into account.

Research Paper:
https://www.nature.com/articles/s43587-025-00986-z