Diseases of Aging Linked to
p21Gene Expression

April 11, 2000; Westport (Reuters Health) - The activation of a single gene, p21, appears to be involved in the pathogenesis of not only cancer but also several age-related diseases, including arthritis, atherosclerosis and Alzheimer's disease, according to a report in the April 11^th issue of Proceedings of the National Academy of Sciences.

"This gene gives rise to a protein that acts as a brake to stop cells from growing," Dr. Igor B. Roninson, of the University of Illinois at Chicago, told Reuters Health in an interview. Normally the protein is produced when cells are damaged or become senescent, he said, explaining that he and his colleagues developed a technique that allowed them to turn the p21 gene off and on in human cells. When the gene was turned on, the cells looked like senescent cells, he said.

The researchers used cDNA microarray technology to see which genes are inhibited and induced when p21 is activated. "What we got were very striking patterns," Dr. Roninson said. They observed that expression of p21 inhibited a set of genes involved in several cellular processes, including mitosis, DNA replication, segregation, and repair. Conversely, many of the genes induced by p21 secrete proteins involved in disease, Dr. Roninson said.

For example, when the gene APP is induced by p21, it produces the beta-amyloid peptide, which forms amyloid plaques that are a hallmark of Alzheimer's Disease. The p21 gene is also linked to the induction of the inflammatory protein SAA, which is involved in the development of atherosclerosis, osteoarthritis, and rheumatoid arthritis, according to the report. The p21 gene also induces several other proteins associated with atherosclerosis, cancer, Alzheimer's Disease, and aging.

"The effects of p21 on gene expression may be a contributing factor to the development of various age-related diseases," Dr. Roninson said in the interview. "This is something we are looking to confirm." According to Dr. Roninson, the findings provide a rationale for developing drugs that block the effects of p21. "We hope that these drugs might be able to have anti-cancer activity and also help slow down different age-related diseases," he said.

Ref. Proc Nat Acad Sci USA, Vol. 97, pp. 4291-4296 (2000).