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Ben-Gurion University Researchers Show Decrease in SIRT6 Protein Likely Cause of Neurodegenerative Diseases in Seniors

May. 08, 2017

BGU researchers have made progress determining causal factors resulting in neurodegenerative diseases in seniors. Aging is the main risk factor for developing a neurodegenerative disease. Therefore, understanding the aging process can help us comprehend what goes wrong in age-related diseases. The common consensus is that aging is the result of DNA damage accumulation, essentially the body’s failure to implement processes to completely repair its DNA over the years. Sporadic Alzheimer’s disease affects about 50% of people over 90, suggesting that the causes are mainly age related. 

One of the key components in this DNA repair process is SIRT6. BGU researchers have determined in mouse models that high levels of SIRT6 contribute to DNA repair while low levels permit DNA damage accumulation. The researchers tested their hypothesis regarding a series of neurodegenerative diseases that includes Alzheimer’s and found that a decrease of the SIRT6 protein results in increased DNA damage and preceded other markers of encroaching disease such as hyperphosphorylated Tau. SIRT6 was nearly completely absent in Alzheimer’s disease patients. 

These promising new findings Neuroprotective Functions for the Histone Deacetylase SIRT6” were published recently in Cell ​Reports​

Lead author Dr. Deborah Toiber (pictured above) of the Department of Life Sciences in the Faculty of Natural Sciences, “If a decrease in SIRT6 (and lack of DNA repair) is the beginning of the chain that ends in neurodegenerative diseases in seniors, then we should be focusing our research on how to maintain production of SIRT6 and avoid the DNA damage that leads to these diseases.” 

Toiber’s lab is one of only a handful worldwide looking at the effects of SIRT6 in the brain, and possibly the only one focusing on its connection to neurodegenerative diseases. Born and raised in Mexico City, Toiber completed her post-doc at Harvard University and joined the BGU faculty in recent years. 

Toiber is the incumbent of the Zehava and Chezy Vered Career Development Chair in Alzheimer's and Neurodegenerative Diseases.

This work was supported by the Israeli Ministry of Science, Technology and Space.