Tick, tock, you’re dead

It’s said that if you’re lucky, you’ll grow old gracefully, accepting with aplomb the wrinkles, hair loss, and organ failure that come with age. However, these characteristics may not be the result of natural wear and tear. A new study published 19 July in Genes and Development suggests that how we age may be linked to a gene that, until now, was only thought to be involved with the body’s internal clock. Scientists first noticed connection between aging and circadian rhythms in mice bred to lack a gene known as BMAL1. BMAL1 is part of the molecular machinery that keeps the body in synch with the daily rising and setting of the sun, and mice that lack the gene had irregular activity patterns–using their running wheel at strange times of day, for example. The mice also seemed to die a lot sooner than normal mice, but until now, no one had done a formal study to investigate why.

To see if BMAL1 plays a role in aging, Marina Antoch, a molecular biologist at the Lerner Research Institute in Cleveland, Ohio, and her team observed a group of 30 BMAL1 knockout mice. The knockout mice lived only half as long as 30 normal mice did, the researchers found. They also found that the knockout mice aged at an accelerated rate: By 18 weeks of age, the knockouts had lost a significant amount of fat, muscle, and bone mass. They also exhibited organ shrinkage in their spleens, kidneys, hearts, lungs, and testes–all signs of aging. And, like older humans, the BMAL1 mice lost hair and developed cataracts in one or both eyes.

Further experiments showed that mice lacking BMAL1 had anywhere from 10 to 50 percent higher tissue concentrations of harmful reactive species of oxygen and nitrogen, which are associated with the aging process. This finding suggests BMAL1 may help stave off aging by preventing the build-up of these species, says co-author Roman Kondratov, a molecular biologist also at the Lerner Research Institute. “I think the next step is really tying this observation to the clock function of BMAL1,” says cardiologist Garret FitzGerald of the University of Pennsylvania School of Medicine in Pittsburgh. If there is a functional link, he says, we may someday be able to manipulate our circadian clocks to prevent the ill effects of old age.

August 14, 2006

Original web page at ScienceNow