Sci. Aging Knowl. Environ., 15 December 2004
Young blood helps old muscle heal
WASHINGTON, D.C.--According to at least one legend, 1000-year-old vampires assure themselves long, healthy lives by drinking the blood of young victims. Similarly, old mice that share the blood of young mice repair injuries with youthful prowess, according to research presented here 8 December 2004 at the American Society for Cell Biology Annual Meeting. The results suggest that youthful rodents pump a compound into the blood that keeps tissue-replenishing cells active.
As animals age, they lose the ability to patch wounds. For example, in young mice with damaged muscles, satellite cells, the stem-cell-like progenitors of muscle fiber, snake from healthy tissue into the injury and restore it. But old animals replace hurt muscle with scar tissue--the satellite cells don't muster. Conboy and colleagues wondered whether the problem arises because old animals harbor fewer satellite cells, but they found the same number of such cells in the muscle of old and young animals. However, five times as many satellite cells from young mice reproduced compared to those in the aged animals.
In youngsters, injuries stimulate healthy muscle and satellite cells to make a molecule called Delta. Delta then turns on Notch, a gene whose product prompts growth of new muscle fiber (see Miller and Emerson Perspective and "Many Roads to Ruin"). In old rodents, cells did not make Delta after an affront to muscle, the researchers found. To determine whether Notch could still be activated, they then added to cultures of muscle satellite cells from the elderly animals a different molecule that cranks up Notch. Reproduction increased fourfold.
To determine whether Notch's doldrums could be overcome, the researchers sewed pairs of mice together to create Siamese twin-like rodents. Called parabiosis, this method allows blood to flow between animals. The researchers made doublets of old mice and joined old to young animals. Then they injured a muscle in one animal of each pair. Delta activity in the muscle cells of old mice joined to young mice increased about fivefold compared to that of old mice joined to old mice, and the injury healed rather than scarred. The observation suggests that young mice produce a molecule--not Delta, which can't travel from one cell to another--that activates Delta, and thus satellite cells, in old muscles. The researchers also noted that young muscle did not recover as well when bound to an old animal, suggesting that aged animals make a compound that inhibits healing.
"One of the fundamental problems in aging is whether [the process] is driven [from within cells] or whether systemic physical changes play a role," says stem cell researcher Sean Morrison of the University of Michigan Medical School in Ann Arbor. "In this case, it appears [that] both play a role": Muscle cells lose Delta and the blood carries a healing inhibitor. He adds that "using parabiosis to address this question is a really creative solution to dissecting" aging in muscle cells. Now, if researchers can identify youth's secret flowing through the body, vampires won't be the only ones drinking to long life.
December 15, 2004
Science of Aging Knowledge Environment. ISSN 1539-6150