Fountain of Youth?

Fountain of Youth?

Forget the eye cream and aerobics classes – new research out of Dr. Darren Baker’s lab at the Mayo Clinic suggests that a better understanding of the molecular mechanisms of aging may one day result in treatments that intervene in the root causes of age-related degeneration, rather than simply treat the symptoms.

Dr. Baker’s research focuses on a protein known as p16INK4A. This is a protein that is produced when cells approach the upper limit of the number of times that they can divide – a number known as the Hayflick limit, thought to be an anti-cancer mechanism in cells but also associated with cell senescence – aging and death. The challenge has been to figure out a way around this Hayflick limit without inducing cancer.

The Baker lab may have found such a workaround. Studying a type of mouse born with progeria – a condition that causes the mice to age much more rapidly than normal – Dr. Baker’s group observed that not only do rapidly aging cells deteriorate, but that they also seem to have adverse affects on other, healthy cells nearby. This led them to hypothesize that if they could somehow selectively kill the most rapidly aging cells, the mice would get two benefits for the price of one.

Since the most rapidly aging cells are also the first cells to start producing p16INK4A, this protein could also serve as a targeting mechanism for the selective destruction of rapidly aging cells. Dr. Baker’s team genetically engineered a strain of progeriatric mice that would produce a second protein whenever the production of p16INK4A increased. This second protein is harmless, but is converted into a toxic form when the mice are administered an activating drug. This toxic form results in the death of the cells that contain it – but not the surrounding healthy cells.
The results of this experiment, published last month in Nature, were nothing short of astounding. The engineered mice exposed to the activating drug showed markedly fewer signs of aging – less muscle wasting, fewer cataracts, better performance on treadmill tests. These results offer the tantalizing possibility that there may in fact someday be a silver bullet to selectively destroy aging cells in humans, leaving behind stronger, healthy cells and tissues.