It is not drinking some magic liquid from a fountain of youth that could reverse aging but – according to scientists at Ben-Gurion University (BGU) of the Negev in Beersheba – identifying genes that control aging and then reverse damage to the genetic material.
Dr. Debra Toiber of the department of life sciences at BGU’s Faculty of Natural Sciences and the Zlotowski Center for Neuroscience focused on one key gene called SIRT6. “My research for the last several years has focused on unlocking secrets of this gene, which we discovered plays a number of prominent roles in aging.”
Brain-specific SIRT6 mice present increased DNA damage, learning impairments and neurodegenerative phenotypes, placing this gene as a key protein in preventing neurodegeneration, they wrote. In the aging brain, SIRT6 levels and activity decline, which is especially prominent in Alzheimer’s patients.
In her latest study, performed on lab mice and published in the journal Aging under the title Aging and pathological aging signatures of the brain: Through the focusing lens of SIRT6,” Toiber and her team identified a handful of genes that are affected in pathological aging but not in normal aging. They found that from these genes, there are some that can be reversed by interventions such as calorie restriction.
During aging, there is an increase in the incidence of several age-related diseases including neurodegeneration (the breakdown of neurons) in which aging itself is the main risk factor, the team wrote. “Technological advances over the last centuries have drastically changed the environment in which humans evolved. As a result, the mean life expectancy increased from 40 to 45 years before the modern era to 78.8 nowadays, mostly due to decreased rates of infant mortality, improved medical care and favorable environmental conditions.”
Suddenly (in evolutionary terms), aging people have to deal with new health threats and the maintenance of organismal function for longer times, as more persons survive much longer than before. Among the few successful treatments to delay aging, restricting how much one eats has been proven successful in extending lifespan and alleviate some of the detrimental effects of aging, such as cardiovascular disease, insulin resistance and increased oxidative damage. The effects of calorie reduction are documented in various model organisms including worms, flies, mice and the primate rhesus monkey, suggesting that these effects are translatable into humans. Nevertheless, the underlying mechanism is still under debate.
From previous studies, they found that that SIRT6 plays a vital instrumental role in DNA repair and serves as a first responder in DNA double-strand breaks, immediately going to work but also signaling to other proteins to come help repair the damage. Toiber believes one of the main causes of aging is the accumulation of unrepaired DNA damage that can lead to neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases.
Since there are many changes in aging and in these pathologies, the Toiber group compared SIRT6-impaired mice to regular mice, both the same age and compared to older mice. Using their knowledge of SIRT6, they were able to narrow these changes down and discern the genes that could predict whether a brain is moving towards healthy aging or pathological aging. In addition, they were able to determine which genes are better candidates for targeted therapies – those whose damage can be reversed. In the future, a test for changes in a set of genes could tell us whether we are heading towards healthy aging, she concluded.