Thursday, 31 January 2013

SIRT3 reverses the effects of ageing

A very interesting study was published today, possibly bringing scientists a step closer to reversing the effects of age-related degeneration. Specifically the study, conducted by biologists from the University of California, gives us a deeper insight of the mechanisms associated with ageing and describes how the SIRT3 gene may be manipulated for reversing the molecular clock of stem cells. The study's findings have great implications in the development of new treatments for age-related conditions and perhaps the development of a therapy for reversing the effects of ageing.

SIRT3 is a protein of the mammalian sirtuin family of proteins, encoded by the SIRT3 gene. Sirtuins are located in cell's mitochondria. Previously published literature strongly suggests that there is a  link between SIRT3 and ageing. One interesting finding regarding the SIRT3 gene is that it is activated by low calorie diets, extending for some reason the mean lifespan of various species.

As of today, there was no other study examining whether it is possible to employ sirtuins to reverse the results of ageing or not.

computer generated image of the SIRT3 protein
Computer generated imaged of SIRT3

The research group, led by Danica Chen, decided to test if SIRT3 holds the key for creating a "youth fountain". To better figure the role of SIRT3 in ageing, the researchers decided to examine mouse hematopoietic stem cells (HSCs), as these cells are highly enriched in SIRT3 . To do so, they divided their mice into two groups. One group comprised of  normal, healthy mice and one group that had the SIRT3 gene deactivated. 

At first, no differences were noted between the two groups. But time brought some very interesting revelations. Reportedly after two years, the SIRT3 deficient mice had way less HSC concentration levels than the healthy ones did. As a result their ability to generate new blood cells was greatly hindered.

According to the research team, young cells have relatively low levels of oxidative stress which is the result of of harmful metabolic byproducts. While still young, the body can easily cope with this burden but as time passes, more and more harmful byproducts are accumulated. Chen explains that as we age our SIRT3 levels significantly drop, indicating that these proteins somehow help our body to deal with the amassed amounts  oxidative stress.

To prove this hypothesis, the researchers increased the SIRT3 levels in the HSCs of the aged mice. As expected, the stem cell population was rejuvenated and blood cell production greatly increased.

Chen says that much more research is needed to find whether SIRT3 can be used for prolonging our lives. She adds that this is not the primary goal of the study, as the findings have all kinds of implications for many age related diseases like Parkinson's and Alzheimer's disease.

Katharine Brown, the study's co-lead author, adds that SIRT3 proteins act as a tumor/cancer suppressor. According to her, this feature is very important because a possible future SIRT3-based rejuvenation treatment would carry minimal ,if any, risks of inducing cancer related diseases.

Brown K, Xie S, Qiu X, Mohrin M, Shin J, Liu Y, Zhang D, Scadden DT, & Chen D (2013). SIRT3 Reverses Aging-Associated Degeneration. Cell reports PMID: 23375372

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