Gene Called Link Between Life Span and Cancers

The New York Times describes some research studies that suggest that a gene switches off stem cells as a person ages to combat cancer. Excerpts below.

Link: Gene Called Link Between Life Span and Cancers - New York Times

Biologists have uncovered a deep link between life span and cancer in the form of a gene that switches off stem cells as a person ages.

The critical gene, well known for its role in suppressing tumors, seems to mediate a profound balance between life and death. It weighs the generation of new replacement cells, required for continued life, against the risk of death from cancer, which is the inevitable outcome of letting cells divide.

To offset the increasing risk of cancer as a person ages, the gene gradually reduces the ability of stem cells to proliferate.

The new finding, reported by three groups of researchers online yesterday in Nature, was made in a special breed of mice that lack the pivotal gene, but is thought likely to apply to people, as well.

The finding suggests that many degenerative diseases of aging are caused by an active shutting down of the stem cells that renew the body’s various tissues and are not just a passive disintegration of tissues under daily wear and tear. “I don’t think aging is a random process — it’s a program, an anticancer program,” said Dr. Norman E. Sharpless of the University of North Carolina, senior author of one of the three reports.

The other senior authors are Drs. Sean J. Morrison of the University of Michigan and David T. Skadden of the Harvard Medical School.

The full implications are far from clear, but the finding that the cells are switched off with age does not seem too encouraging for researchers who hope to use a patient’s own adult stem cells to treat disease. That result may undercut opponents of research on human embryonic stem cells who argue that adult stem cells are enough to build new tissue.

Dr. Sharpless said his finding showed the need to pursue both types of research. The gene in the finding has the unmemorable name of p16-Ink4a. It plays a central role in the body’s defenses against cancer, and it produces two quite different proteins that interact with the two principal systems for deciding whether a cell will be allowed to divide.

One of the proteins had also been noted to increase substantially with age. The cells of a 70-year-old produce 10 times as much of the Ink4 protein as those of a 20-year-old, Dr. Sharpless said.

The researchers assume, but have not yet proved, that the increasing amounts of Ink4 as a person ages will thrust the stem cells into senescence, meaning that they can never divide again. The evolutionary purpose is evidently to avert the risk that a damaged stem cell might evade controls and proliferate into a tumor.

One implication is that therapists who hope to increase longevity have to tackle a system that may be hard to cheat. An intervention that reduces Ink4 production to prevent the age-related decline of stem cells will also increase the risk of cancer.