Turn off aging and reverse it

A single gene mutation leads to lifespan extension



SIRT3 is the anti-aging gene that could make a real difference in people’s lives, even sooner than they might suspect. SIRT3 stands for sirtuin (silent information regulator 2 homolog) 3 (S. cerevisiae). It is a yeast-based protein in DNA. University of California at Berkeley researchers infused aging mice stem cells with SIRT3 longevity genes and discovered improved blood cell production, indicating rejuvenation.

“We already know that sirtuins regulate aging, but our study is the frst one demonstrating that sirtuins can reverse aging-associated degeneration,” said study principal investigator Danica Chen, UC Berkeley assistant professor of nutritional science and toxicology, whose report appeared online in the journal Cell Reports. “This opens the door to potential treatments for agerelated degenerative diseases.”

Chen’s research refects a new thinking in anti-aging medicine over the last two decades. Aging is not uncontrolled or random but a process regulated by genes that can be turned on, off, modifed or rejuvenated.

“Studies have already shown that even a single gene mutation can lead to lifespan extension,” said Dr Chen. “The question is whether we can understand the process well enough so that we can develop a molecular fountain of youth. Can we actually reverse aging? This is something we’re hoping to understand and accomplish.”

As part of mitochondria, the cell’s energy factories, SIRT3 genes turn on in response to low-calorie diets. These diets extend lifespan in animal species and in at least one human study on males associated with SIRT3 alleles.

Sarah Yang in Science Daily explains, “Surprisingly, among young mice, the absence of SIRT3 made no difference. It was only when time crept up on the mice that things changed. What is behind the age gap? It appears that in young mice, the blood stem cells are functioning well and have relatively low levels of oxidative stress, which is the burden on the body that results from the harmful byproducts of metabolism. At this youthful stage, the body’s normal antioxidant defenses can easily deal with the low stress levels, so differences in SIRT3 are less important.”

But with age, there is an increase in oxidative stress and the body doesn’t remove it as well. 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 antioxidant system. However, SIRT3 levels also drop with age, so over time the system is overwhelmed.

The next step is to see whether overexpression of SIRT3 can prolong life. Study co-lead author Katharine Brown, who conducted the research as a UC Berkeley PhD student in Chen’s lab, said SIRT3 has some potential in this regard. “Other researchers have demonstrated that SIRT3 acts as a tumor suppressor. This is promising because, ideally, one would want a rejuvenative therapy which could increase a protein’s expression without increasing the risk of diseases like cancer.”

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