University scientists have unlocked a clue to why humans age the way they do. In a study that clarifies the link between stem cells, cancer and aging, researchers have identified an entire set of genes that regulate stem cell division with age.

The study, to be published today in the peer-reviewed journal Cell, found that the same genes that switch off stem cell division are already well known to guard against cancer, implying that stem cells also shut down as they age.

In a paper published two years ago in the peer-reviewed journal Nature, the Director of the Center for Stem Cell Biology Sean Morrison, who headed the research and is the senior author of the paper, and his lab identified one of the tumor suppressing genes – Ink4a – that also regulates stem cell division as mice get older.

After three years of experimenting on mice brain cells, scientists now know the sequence of genes that triggers Ink4a. The pathway is presumably the same in humans as in mice, since humans have the same four genes.

Morrison’s lab discovered that because the mechanisms causing stem cell division are the same ones hijacked by cancerous cells, tumor suppressor genes in mice also terminate adult stem cell division.

“By turning those mechanisms up, you probably reduce the incidence of cancer as you age,” he said. “The bad news is that they start to shut down the function of your normal stem cells because stem cells use those same mechanisms to divide.”

The study has identified a number of genes that are involved in slowing down adult stem cell regeneration as a cancer defense mechanism.

“These cells function as part of an entire pathway – some go up, some go down as you age – but that work together to reduce the number of stem cells in the brain and how active they are,” Morrison said.

As humans grow older, the body becomes less resilient. Injuries and illnesses become more perilous because adult stem cells found in specialized tissue don’t regenerate as well. Age also increases a person’s likelihood of developing cancer, which is caused when cells divide out of control. As it grows older, the human body combats the risk by turning on tumor suppressor genes, or genes that stop excess cells from dividing.

“All these things have been known for a long time,” said Morrison. “What has not been known is why. Why is it that older tissues regenerate themselves less well and that you make fewer brain cells in particular as you get older?”

Morrison said the discovery also points to why adult stem cells can’t be used in place of embryonic stem cells, a request often made by opponents to embryonic stem cell research.

“The mechanisms we’re talking about here probably don’t exist in embryonic stem cells,” said Morrison. “So embryonic stem cells effectively don’t age – they’re immortal, whereas adult stem cells have a limited number of specialized cells because they can age.”

A measure on the ballot in November seeks to remove some of the bans around human embryonic stem cell research by granting scientists access to discarded embryos from fertility clinics for research.

Morrison said prior to the study, scientists didn’t know why adult stem cells differed from embryonic stem cells, but this study is the first step in identifying how they differ.

The research was sponsored by the National Institute of Health and the Howard Hughes Medical Institute.