Sirtuins function generally as a cellular molecular switch sitting at the crossroad between metabolism, mitochondrial function, anti-oxidation and DNA transcription and repair.
In the current study out of Harvard University, researchers looked at and manipulated the SIRT3 gene and determined its role in aging and regeneration.
In particular they studied adult mouse blood stem cells which function normally to repopulation the blood cell lines.
First they analyzed the stem cells of mice who had the SIRT3 gene knocked out. In young mice the stem cells behaved the same in normal and SIRT3 deficient mice. However once they reached more advanced ages the SIRT3 deficient mice stem cells became significantly impaired in their ability to regenerate new blood cells.
They found in young mice, oxidative stress levels in the cells were low so they could be eaily dealt with. With age however oxidative stress levels increased, requiring the help of SIRT3 to bolster intracellular antioxidant defenses. So age it appears both increases oxidative stress and decreases the mechanisms to deal with it.
“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,” said lead author Danica 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.”
In the particularly important part of the experiment, the researchers attempted to see if increasing SIRT3 levels in aged stem cells would improve function.
They induced over-expression of SIRT3 in aged mouse cells by transfecting the gene into the cells using a virus. This treatment rescued the effect of age – they observed a dramatic 5-fold increase in regenerative capacity. This study thus confirms increasing SIRT3 expression can restore youthfulness to old cells.
The authors conclude “evidence is emerging to indicate that mammalian sirtuins slow aging, our study demonstrates that a sirtuin can also reverse aging-associated degeneration.”
