Postponing Red-Cell Retirement: Can Aging Blood Cells Get a New Lease on Life?

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Postponing Red-Cell Retirement

Each day, without fanfare, an average adult gives birth to about 200 billion new red blood cells. That amounts to 2.3 million cells squeezing through microscopic, bony "birth canals" every second, emerging from their nurturing birthplace in marrow to make their working debut in the bloodstream. Dutifully they circulate through the body, hauling oxygen atoms to distant tissues in need of the life-giving gas.

Equally impressive and perhaps less appreciated is the daily disappearance of another 200 billion red cells. And not just any 200 billion. For the most part, the body picks and chooses from the roughly 25 trillion circulating red cells those 1 percent that have enjoyed long, full lives. Having outlived their usefulness and thus their welcome after 120 days or so on the job, these aging couriers become targets of a poorly understood but impressively efficient biological mechanism that rips them open, recycles their valuable, ironrich cores and sends the remaining cellular remnants to the liver and kidneys for disposal.

Were it not for this constant scavenging of older red blood cells, says Philip S. Low, a blood chemist from Purdue University at West Lafayette, Ind., "our blood would be thick as concrete in a couple of weeks."

But when the body cleans house, how does it know which red cells to spare and which to sweep away? Do some cells display molecular or behavioral hallmarks of old age that the body recognizes as signs of senescence?

Scientists seek answers to these questions out of a desire to tinker with the mechanisms of cellular death, not just in the blood but throughout the body. Red cells resemble most other cell types in their basic membrane structure but are more easily obtained than many other types. By investigating the tools the body uses to recognize and remove aging blood cells, scientists may eventually gain some control over these biological housekeeping duties elsewhere in the body -- perhaps slowing cell death or at least preventing the accelerated removal of healthy cells that occurs in certain diseases.

Even if the work proves applicable only to blood cells, researchers say, such an ability could offer immense benefits to the blood banking industry and to patients who today need frequent transfusions. "The hope," says Low, "is that we can modify or affect the aging process," to prolong the life of red cells either in blood banks or within the body.

But while scientists have made significant progress in understanding red-cell senescence, they have yet to agree upon any one molecular "cause" of cell aging or even a marker that points to cells past their prime, says Margaret R. Clark, a hematologist at the University of California, San Francisco. "We still don't know how to recognize aging red blood cells very well at all," she says. And so far, the markers researchers have proposed as signposts of red-cell senescence reflect "more wishful thinking than hard evidence."

A fundamental problem stalls scientists in their endeavor to understand cell senescence. In order to identify molecular landmarks of the aging process, researchers must get a relatively pure population of aged cells for comparison with younger cells. And in order to pull aside such a population, they must first have a way of identifying them and separating them from their younger counterparts. In short, without markers of aging, it's difficult to find markers of aging.

Hematologists have long relied on measures of individual cell density and size to obtain populations of older red blood cells. "The dogma has been that as cells age they become more dense and smaller," says George L. Dale of the Scripps Clinic and Research Foundation in La Jolla, Calif. Upon separating such cells, researchers have identified a handful of alterations that less dense, presumably younger cells seem to lack.

But many scientists think the cell populations culled through the density separation technique reflect more age diversity than previously assumed. …