Aging and pathological aging signatures of the brain: through the focusing lens of SIRT6
| العنوان: | Aging and pathological aging signatures of the brain: through the focusing lens of SIRT6 |
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| المؤلفون: | Alfredo Garcia Venzor, Debra Toiber, Ekaterina Khrameeva, Anastasia Golova, Daniel Stein, Monica Einav, Shai Kaluski, Amir Mizrahi, Adam Saretzky, Zeev Slobodnik |
| المصدر: | Aging Aging (Albany NY) |
| بيانات النشر: | Impact Journals, LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | SIRT6, Aging, Calorie restriction, Gene Expression, Biology, YY1, Transcriptome, Mice, Gene expression, Transcriptional regulation, medicine, Animals, Humans, Sirtuins, Aging brain, YY1 Transcription Factor, Mice, Knockout, Neurodegeneration, neurodegeneration, Brain, Neurodegenerative Diseases, Cell Biology, medicine.disease, transcription regulation, Neuroscience, Research Paper |
| الوصف: | Brain-specific SIRT6-KO mice present increased DNA damage, learning impairments, and neurodegenerative phenotypes, placing SIRT6 as a key protein in preventing neurodegeneration. In the aging brain, SIRT6 levels/activity decline, which is accentuated in Alzheimer’s patients. To understand SIRT6 roles in transcript pattern changes, we analyzed transcriptomes of young WT, old WT and young SIRT6-KO mice brains, and found changes in gene expression related to healthy and pathological aging. In addition, we traced these differences in human and mouse samples of Alzheimer’s and Parkinson’s diseases, healthy aging and calorie restriction (CR). Our results define four gene expression categories that change with age in a pathological or non-pathological manner, which are either reversed or not by CR. We found that each of these gene expression categories is associated with specific transcription factors, thus serving as potential candidates for their category-specific regulation. One of these candidates is YY1, which we found to act together with SIRT6 regulating specific processes. We thus argue that SIRT6 has a pivotal role in preventing age-related transcriptional changes in brains. Therefore, reduced SIRT6 activity may drive pathological age-related gene expression signatures in the brain. |
| تدمد: | 1945-4589 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbfa85d6caee51750ed596ffd0836d18 https://doi.org/10.18632/aging.202755 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cbfa85d6caee51750ed596ffd0836d18 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19454589 |
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