What Old Mice Taught Scientists About Cancer<\/p>\n
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.<\/p>\n
Old mice develop fewer and smaller lung tumors (red) than younger animals in a cancer model. The findings suggest that, in very old animals or humans, the aging process suppresses cancer formation. (CREDIT: Emily Shuldiner) <\/p>\n
After scientists activated a cancer-driving KRAS mutation<\/a>, 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.<\/p>\n \u201cIt\u2019s a striking finding,\u201d said Monte Winslow, an associate professor of genetics and pathology. \u201cWe would expect that older animals would get more and worse cancers, but that\u2019s not at all what the study found.\u201d<\/p>\n The results matched a pattern seen in people over 85, whose cancer rates<\/a> 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.<\/p>\n Fewer Tumors and Slower Growth in Older Lungs<\/p>\n 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.<\/p>\n 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.<\/p>\n \u201cAging is a systemic change to your body, but most cancer studies in mice are conducted on younger animals,\u201d said former graduate student and study lead author Emily Shuldiner. \u201cWhen we introduced the same lung cancer-causing mutations in young and old mice, the young mice develop more, faster growing tumors.\u201d<\/p>\n Her work, published in Nature Aging, shows that aging does not simply push tissues toward cancer. Instead, older tissues can resist tumor development<\/a> in ways younger tissues cannot.<\/p>\n How Age Weakens the Impact of Tumor Suppressor Loss<\/p>\n 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\u2019 influence, the team used CRISPR gene editing to inactivate 25 tumor suppressors one by one.<\/p>\n 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.<\/p>\n Pathway activity scores comparing PTEN-deficient (sgPten) to wild-type (sgInert) for young and aged cancer cells. Positive scores (red) indicate that a pathway is more active with Pten inactivation; negative scores (blue) indicate that a pathway is less active with Pten inactivation. (CREDIT: Nature Aging) <\/p>\n 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.<\/p>\n \u201cPTEN inactivation stood out as having a much stronger effect in young mice,\u201d Shuldiner said. \u201cIt suggests that the effect of any given mutation, or the efficacy of cancer therapies<\/a> targeted at specific mutations, might be different in young versus old people.\u201d<\/p>\n Aging Leaves a Mark Even on Cancer Cells<\/p>\n 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.<\/p>\n \u201cWe found that patterns known to be associated with aging were still present in the cancer cells from old mice,\u201d Shuldiner said. \u201cThis was not an obvious finding because cancer cells are rapidly dividing.\u201d<\/p>\n 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<\/a>, suggesting that PTEN loss resets whole neighborhoods of tissue.<\/p>\n Uniform Manifold Approximation and Projection (UMAP) embedding of cells colored by whether they were sorted as \u2018neoplastic cells\u2019 or \u2018bulk cells\u2019. (CREDIT: Nature Aging) Rethinking the Link Between Age and Cancer<\/p>\n 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.<\/p>\n \u201cThe implications of this story could be huge,\u201d said Dmitri Petrov, professor of biology. \u201cMaybe aging<\/a> has a beneficial side to it that we could harness for better therapies.\u201d<\/p>\n Winslow agrees. \u201cWe develop these animal models of cancer with an eye to developing new treatments for patients,\u201d he said. \u201cBut 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.\u201d<\/p>\n![\"\"](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2025\/11\/monte-winslow.jpeg\")
Monte Winslow, PHD![\"\"](\"https:\/\/www.newsbeep.com\/au\/wp-content\/uploads\/2025\/11\/dmitri-petrov.jpeg\")
Dmitri Petrov, PHD<\/p>\n