Here is another study on the subject of aging! One more piece of the puzzle! 😊
"... 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. ... found that SIRT6 is a key regulator of mitochondrial function in the brain ...
Focused on a protein called SIRT6, she has discovered that it seems to have remarkable properties. Its absence seems to downgrade DNA repair significantly. ... found that SIRT6 is a key regulator of mitochondrial function in the brain ...
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. ..."
From the abstract:
"The SIRT6 deacetylase has been implicated in DNA repair, telomere maintenance, glucose and lipid metabolism and, importantly, it has critical roles in the brain ranging from its development to neurodegeneration. Here, we combined transcriptomics and metabolomics approaches to characterize the functions of SIRT6 in mouse brains. Our analysis reveals that SIRT6 is a central regulator of mitochondrial activity in the brain. SIRT6 deficiency in the brain leads to mitochondrial deficiency with a global downregulation of mitochondria-related genes and pronounced changes in metabolite content. We suggest that SIRT6 affects mitochondrial functions through its interaction with the transcription factor YY1 that, together, regulate mitochondrial gene expression. Moreover, SIRT6 target genes include SIRT3 and SIRT4, which are significantly downregulated in SIRT6-deficient brains. Our results demonstrate that the lack of SIRT6 leads to decreased mitochondrial gene expression and metabolomic changes of TCA cycle byproducts, including increased ROS production, reduced mitochondrial number, and impaired membrane potential that can be partially rescued by restoring SIRT3 and SIRT4 levels. Importantly, the changes we observed in SIRT6-deficient brains are also occurring in aging human brains and particularly in patients with Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic lateral sclerosis disease. Overall, our results suggest that the reduced levels of SIRT6 in the aging brain and neurodegeneration initiate mitochondrial dysfunction by altering gene expression, ROS production, and mitochondrial decay."
Fig. 1: SIRT6 regulates gene expression levels
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