|Dark brown staining indicates the prevalence of p53 in the oral tissue of six individuals, ranging from age 28 (upper left) to 74 (lower right).
Image: Dr. Reuben Kim
Researchers at UCLA have found that a protein that serves as a suppressor of cancer diminishes in skin and mouth epithelial cells as the human body ages. No-Hee Park, DMD, PhD, dean of the UCLA School of Dentistry, and his research team have been studying p53, a tumor-suppressor protein known as “the guardian of the genome” because of its involvement in DNA repair, cell cycle regulation and cellular deterioration.
“Looking at ways to maintain levels of p53 as one ages may provide a therapeutic clue to preventing cancer development,” says Dr. Park, who is also a distinguished professor in the departments of dentistry and medicine at UCLA.
Previous studies have shown that p53 accumulates in large quantities as connective tissue cells, called fibroblasts, age and stop dividing. It has been believed that the accumulation of p53 causes cells to stop dividing, which prevents out-of-control cells from growing into tumors.
The researchers found that in epithelial cells lining the skin and the mouth, the level of p53 is reduced rather than enhanced when cells age. Epithelial cells line the major cavities of the body, including most organs, such as the mouth, stomach, small intestine, kidney and pancreas. These cells have a set level of p53 that provides protection from environmental factors and ensures their wellbeing. With less p53, older epithelial cells have a harder time maintaining the integrity of their genetic material when they encounter carcinogens, which allows cancer to develop.
Dr. Park and his team also reported that in humans, the level of p53 in skin and mouth epithelial cells decreased with age by epigenetic (external and environmental) factors, not by the changes of the p53 DNA sequence. Because some 90 percent of human cancers originate from epithelial cells, this may account, the researchers suggest, for increased incidence of skin and oral cancers in elderly patients.
“Regulation of p53 during Senescence in Normal Human Keratinocytes,” Aging Cell, July 2015