New research uncovers method to prevent DNA breakdown, aging - study

Women and men are paying high prices for anti-aging creams, plastic surgery, gym memberships, exercise machines and more to look younger – but what does science have to say about aging? 

Dr. Debra Toiber of the life sciences department at Ben-Gurion University of the Negev in Beersheba has uncovered what seems to be a key preventive measure of the breakdown of DNA, which many believe causes aging and neurodegenerative diseases. 

Focused on a protein called SIRT6, she has discovered that it seems to have remarkable properties. Its absence seems to downgrade DNA repair significantly.

In a new paper published in the peer-reviewed journal Cell Death and Disease under the title “SIRT6 is a key regulator of mitochondrial function in the brain,” she and colleagues Dr. Toiber and others at BGU, Harvard Medical School, and the Skolkovo Institute of Science and Technology, Moscow have found that SIRT6 is a key regulator of mitochondrial function in the brain.

In addition to supplying cellular energy, mitochondria are involved in other tasks such as signaling, cellular differentiation, cell death and maintaining control of the cell cycle and cell growth . 

“Mitochondrial dysfunction is one of the hallmarks of aging and one of the main characteristics of multiple neurodegenerative diseases,” Toiber noted.

“Many defects are observed in the mitochondria’s efficiency during aging; however, what initiates these events is unclear. We found that SIRT6 keeps mitochondria functioning through the transcription regulation of mitochondrial genes.”

The mechanisms of aging

“Aging is a consequence of the dysregulation (poor control) of various self-maintenance mechanisms of a living system,” the team wrote. Aging at the cellular level is accompanied by genomic instability, shortening of the telomeres [the ends of chromosomes] ... and mitochondrial dysfunction, together with a decrease in the efficiency of the DNA repair mechanism.

Moreover, these factors are interconnected.

For example, the shortening of telomeres can lead to mitochondrial dysfunction. Aging involves significant changes in brain structure and functional capabilities. Cognitive decline occurs naturally during aging, but in some cases, it can become pathological, such as in neurodegenerative diseases. Importantly, about 95% of neurodegenerative cases are age-related with no known genetic mutation. Therefore, a better understanding of the aging process in disease development is needed.”

Using transcriptomics (the study of the transcriptome, the complete set of RNA in a given cell population), metabolomics (the large-scale study of small molecules known as metabolites within cells, biofluids, tissues or organisms) and molecular assays (detecting the nucleic acid of the targeted pathogen), she and her team observed that in the absence of SIRT6 in the brain, nuclear-expressed mitochondrial genes are down-regulated (suppressing a response to a stimulus). 

In addition, the number of mitochondria per cell decays; there is an increase in the production of derivatives of molecular oxygen (reactive oxygen species or ROS) and the mitochondrial membrane potential is impaired, causing major metabolic changes. 

This effect is partially the result of SIRT6 regulating the expression of the mitochondrial Sirtuins 3 and 4. Reintroducing SIRT3 and 4 can rescue the membrane potential capacity. Particularly in the brain, during neurodegeneration, mitochondria lose the ability to generate enough Adenosine Triphosphate (ATP), generate toxic ROS, and impair the production of important metabolites for brain functioning. 

“Our results show parallel changes in mitochondrial gene expression induced by the lack of SIRT6 in the brain to the changes observed in aging, Alzheimer's disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS), suggesting that SIRT6 decay in the brain is the driver of these changes,” Toiber concluded.