Humans have been trying to outrun old age for millennia, and new research might give us a step on the Grim Reaper. Scientists have prevented age-related liver decline in mice by restoring a key protein that helps the organ trash used proteins. It's not exactly the fountain of youth, but the findings could shed further light on the biological mechanisms of aging.
Why does our body break down as we get older? Some scientists think that disorders such as heart failure and dementia are caused by rogue molecules called free radicals, which ricochet through the body and wreck proteins. A related hypothesis holds that proteins themselves are the problem: Once they’ve outlived their usefulness, they build up in organs and cause trouble, much like road dust can gum up a car engine.
Focusing on the latter idea, Ana Maria Cuervo, a cell biologist at Albert Einstein College of Medicine in New York City, and colleagues looked at protein buildup in the livers of elderly mice. As the rodents get older, cells in their liver sport less of a receptor called LAMP-2A. Cuervo knew that LAMP-2A acts a bit like a garbage truck, scavenging old proteins from the liver and isolating them in tiny cellular pockets, where they can be destroyed. Was LAMP-2A the key to liver senescence?
To find out, the researchers engineered mice to carry an extra LAMP-2A gene. They turned on the gene when the mice were 11 months old, the equivalent of 40 years in a person. Because the liver is vital for breaking down drugs, the researchers assessed the organ's function by measuring how quickly the mice could metabolize a muscle relaxant. When young, healthy mice are injected with the relaxant, they splay out on the lab table, and it takes about 3 hours for them to get up and start moving again. But even 20-month-old mice, the equivalent of 80-year-old humans, showed this youthful response if they had extra LAMP-2A. Control mice of the same age remained paralyzed for about 6 hours.
The results demonstrate that the debris buildup caused by defective LAMP-2A can cause organ decline in mice, the researchers report online this week in Nature Medicine. "So any means of removing this garbage is going to improve function," Cuervo says. Because humans use a similar system to help clean out their cells, Cuervo says the findings may lead to treatments to keep elderly people's organs in prime condition.
It's an "elegantly designed" study, says biologist Marc Tatar of Brown University. But he notes that researchers should also test whether quantities of proteins that help LAMP-2A with its disposal tasks decline with age. And Douglas Schmucker, a cell biologist at the University of California, San Francisco, says the process should be investigated in other organs.