Most laboratory mice don't live long enough to go bald or grey, but a strain of animals missing an enzyme linked to cellular aging look like they could use a bit of Clairol or Rogaine. In tomorrow's Cell, researchers describe how older mice lacking the enzyme telomerase--which helps protect dividing chromosomes--go prematurely grey and begin to lose their fur. The mice also have more trouble healing skin wounds than their normal counterparts. The observations are the first evidence for how the lack of telomerase affects an aging animal.
Telomerase has been hailed as a potential elixir for eternal youth. It helps to lengthen the telomeres--the proteins and DNA on the ends of chromosomes that prevent dividing chromosomes from fraying--and therefore increases the number of times a cell can divide. Adding telomerase to dividing cells in culture can lengthen their lifespan (ScienceNOW, 13 January 1998), but no one has found a direct link between telomeres and animal aging.
Several years ago, Ronald DePinho of the Dana-Farber Cancer Institute in Boston and his colleagues genetically engineered a strain of mice that lacks telomerase. Laboratory mice have unusually long telomeres, however, so it took several generations of ever-shorter telomeres for the first defect to show up: The mice were infertile.
Now the researchers have studied the effects of shortened telomeres on aging mice. By 18 months--old age for a mouse--the mice from generations 3 through 6 were going grey and balding. When the scientists removed patches of skin, the older ones lacking telomerase healed much more slowly than old mice with normal telomerase or young mice lacking telomerase. The old, telomerase-deficient mice also had weaker immune systems and had more trouble recovering from a dose of chemotherapy that killed blood cells. (Likewise, elderly people suffer more from chemotherapy than the young.) Their younger cousins recovered fine, as did older mice with telomerase intact, but more than half of the aged, telomere-depleted mice died from the treatment.
Although results from mice cannot be extrapolated directly to humans, says Jerry Shay of the University of Texas Southwestern Medical Center in Dallas, the mice "really do show that telomere erosion can lead to things we see in [elderly] humans." The mice, he predicts, are "going to be a very important model for studying aging."