We all know that cancer risk generally increases with age, but did you know that at a very advanced age, this trend might reverse? A recent study conducted on mice reveals surprising biological mechanisms that could explain this counter-intuitive phenomenon.
Researchers at Stanford University observed that very old mice developed significantly fewer lung tumors than their younger counterparts. Not only were the tumors fewer in number, but they also proved to be less aggressive. This discovery challenges the commonly held idea that aging only increases cancer risk. Monte Winslow, associate professor of genetics and pathology, expressed his astonishment at these results that contradict traditional scientific expectations.
The study published in
Nature Aging shows that when researchers introduced the same cancer mutations in young and old mice, the younger animals developed more numerous and faster-growing tumors. Emily Shuldiner, the study's lead author, emphasizes that most cancer research is conducted on young animals, which could distort our understanding of cancer mechanisms in elderly people. This innovative approach required considerable patience, as researchers had to wait nearly two years for the mice to reach an advanced age before inducing cancer.
Measurements taken fifteen weeks after cancer induction revealed dramatic differences. The lungs of young mice showed approximately three times more cancerous tissue than those of older animals. Tumors in young mice were not only more numerous but also significantly larger. These observations suggest that the aging process itself might exert a protective effect against cancer development, a concept that opens new potential therapeutic perspectives.
The study particularly focused on the PTEN gene, a tumor suppressor whose inactivation showed very different effects depending on the animals' age. In young mice, deactivating this gene caused a dramatic increase in tumor development, while in older animals, the effect was much less pronounced. This discovery suggests that the impact of genetic mutations and the effectiveness of treatments targeting these mutations could vary considerably depending on patients' age.
Old mice develop fewer lung tumors (red) and smaller ones than young animals in a cancer model.
Credit: Emily Shuldiner
Analysis of genetic signatures revealed another intriguing phenomenon: cancer cells in old mice retained markers characteristic of aging, even while dividing rapidly. However, when the PTEN gene was inactivated in these older animals, these aging signatures became much less pronounced. Dmitri Petrov, senior co-author of the study, considers the exciting possibility that aging might have beneficial aspects that we could exploit to develop better anti-cancer treatments.
This pioneering research clearly demonstrates that aging can suppress tumor initiation and growth, while modifying the impact of tumor suppressor gene inactivation. It highlights the importance of developing new animal models that incorporate aging effects, to better reflect the reality of cancer in elderly patients and improve the development of more effective therapies.
The aging and cancer paradox
Aging is generally perceived as a risk factor for cancer, as the accumulation of mutations over time logically seems to increase the probability of developing tumors. However, this simplistic view doesn't account for the complexity of biological processes. Recent research reveals that at a very advanced age, the organism might develop protective mechanisms that counterbalance the harmful effects of mutational accumulation.
These protective mechanisms could include changes in the cellular and tissue environment that make tumor growth more difficult. For example, modifications to the extracellular matrix or alterations in cell communication signals could create a less favorable environment for cancer development. These age-related transformations could explain why, after a certain threshold, cancer risk stops increasing.
Understanding this paradox opens innovative therapeutic perspectives. If we manage to identify the biological processes responsible for this natural protection in very elderly people, we could potentially reproduce them in younger patients. This approach would represent a new strategy in the fight against cancer, based on exploiting the organism's natural defense mechanisms.