A genetic variant that is abundant in centenarians is emerging as the longevity gene: it delays aging, reduces inflammation and prolongs healthy life. This ingenious protein could reinforce strategies against senescence.
Researchers at the University of Rochester in New York State have discovered that a genetic variant abundant in centenarians allows for more efficient DNA repair and therefore has potent anti-aging effects.
According to this study, the variant of a gene called SIRT6 would repair DNA double-strand breaks (DSB) more efficiently in species with a longer lifespan.
SIRT6 is a protein involved in the regulation of chromatin, the DNA-protein complex found in our cells, and has also been shown to play a role in metabolism, disease, and aging.
SIRT6 is vital for both normal base excision repair and double-strand break repair of DNA damage, as this damage leads to genomic instability and ultimately contributes to aging. according to the researchers.
Previous research has shown that upregulation of SIRT6 in fruit flies and mice slows aging, decreases inflammation, and extends lifespan, and that this nifty protein called sirtuin it can be promoted in the body through fasting, calorie restriction, and dietary supplements.
Last year, researchers at Bar-Ilan University in Israel were able to not only increase lifespan in mice with SIRT6, but also use it to allow old mice to perform the same level of vigorous activity as their young counterparts, without becoming fragile.
In 2019, Vera Gorbunova, professor of biology at the University of Rochester, and her team showed that an overexpression of the SIRT6 protein leads to a longer life and also that the opposite is true: a deficiency can cause premature aging.
According to other research published last December on the bioRxiv preprint server, centenarians would be carriers of this “longevity gene.”
To reach this conclusion, the researchers compared the genetic sequences of 496 centenarian Ashkenazi Jews and 572 Ashkenazi Jews with no family history of exceptional longevity.
They then identified two new variants of SIRT6, one of which, called centSIRT6was associated with exceptional longevity.
This genetic variant was carried by only 1% of the selected centenarians. However, when they compared this data with that of 150,000 people of different ethnic backgrounds, the scientists found that people who lived longer were more likely to have this centSIRT6 variant.
Although SIRT6 overexpression has been shown to prolong lifespan, the actual underlying cellular mechanisms still need to be unraveled and is further delved into by new research from the University of Rochester that has just been published.
Also led by Vera Gorbunova, like that of 2019, the new research, published in PNAS, analyzes the function of SIRT6 in the fruit fly (Drosophila melanogaster) and examines its role in the regulation of longevity.
This research provides extensive insight into the mechanisms by which SIRT6 overexpression leads to longer life.
It concludes that overexpression of SIRT6 can extend the lifespan and health of flies through increased resistance to oxidative stress and/or reduced protein synthesis.
He adds that SIRT6 increases life expectancy, in part, by opposing the activity of Myc, a regulator of protein synthesis, which is associated with decreased protein synthesis.
A particularly interesting point that emerges from the study concerns the mechanistic target of rapamycin (mTOR) pathway, the journal Longevity Technology highlights.
Inhibition of mTOR is a well-established means of extending lifespan as well and can be induced by rapamycin, as established by research published in the journal Cell Metabolism in January 2010.
As mTOR inhibition also reduces protein synthesis and prolongs lifespan in fruit flies, the authors of the latest research suggest that both the effects of SIRT6 overexpression in fruit flies and treatment should be examined. with rapamycin on lifespan and protein synthesis, to support anti-aging strategies.
Finally, the authors of the new research emphasize that their results highlight the importance of the different SIRT6 activators identified in recent years, and that they are therefore useful for treating age-related diseases and extending the useful life of health. in humans.
And they conclude that the fruit fly may offer a useful model to study these compounds in the aging process and age-related diseases.
Sirt6 regulates lifespan in Drosophila melanogaster. Jackson R. Taylor et al. PNAS February 1, 2022 119 (5) e2111176119. DOI:https://doi.org/10.1073/pnas.2111176119
A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A. Matthew Simon et al. bioRxiv, December 13, 2021. DOI:https://doi.org/10.1101/2021.12.13.472381
Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Ivana Bjedov et al. Cell Metabolism, 2010 Jan;11(1):35-46. DOI: 10.1016/j.cmet.2009.11.010.