Scientists at the University of California, Berkeley, say they’ve been able to turn back the molecular clock by infusing the blood stem cells of old mice with a longevity gene – bringing back the stem cells’ ability to regenerate.
The discovery, they say, is a major advance in the understanding of the molecular mechanisms behind aging. It could help in the development of targeted treatments for age-related degenerative diseases – and possibly lead to general lifespan extension.
The biologists found that SIRT3, one of a class of proteins known as sirtuins, plays an important role in helping aged blood stem cells cope with stress. Infusing the blood stem cells of old mice with SIRT boosted the formation of new blood cells – showing a reversal in their age-related decline.
“We already know that sirtuins regulate aging, but our study is really the first one demonstrating that sirtuins can reverse aging-associated degeneration, and I think that’s very exciting,” says Danica Chen, assistant professor of nutritional science and toxicology. “This opens the door to potential treatments for age-related degenerative diseases.”
SIRT3 is found in a cell’s mitochondria, a cell compartment that helps control growth and death. Previous studies have shown that it’s activated during calorie restriction, which has been shown to extend lifespan in some species.
The researchers studied the function of adult stem cells, which are responsible for maintaining and repairing tissue – a function that breaks down with age. They focused on blood stem cells because of their ability to completely reconstitute the blood system.
In young mice that had the gene for SIRT3 disabled, the absence of SIRT3 made no difference. However, by the time they were two years old, the SIRT3-deficient mice had significantly fewer blood stem cells and a poorer ability to regenerate new blood cells than normal mice of the same age.
“When we get older, our system doesn’t work as well, and we either generate more oxidative stress or we can’t remove it as well, so levels build up,” says Chen. “Under this condition, our normal anti-oxidative system can’t take care of us, so that’s when we need SIRT3 to kick in to boost the anti-oxidant system. However, SIRT3 levels also drop with age, so over time, the system is overwhelmed.”
Boosting SIRT3 levelshad the opposite effect, rejuvenating the aged blood stem cells and leading to improved production of blood cells.
It remains to be seen whether over-expression of SIRT3 can actually prolong life.
“Studies have already shown that even a single gene mutation can lead to lifespan extension,” says Chen.
“The question is whether we can understand the process well enough so that we can actually develop a molecular fountain of youth. Can we actually reverse aging? This is something we’re hoping to understand and accomplish.”