Similar Datasets
Project description:RNA-sequencing of livers in wt and sirt6-tg mice
| PRJNA662946 | ENA
Project description:The significant increase in the human life-span during the last century confronts us with great medical challenges. To answer them, one must understand and control the mechanisms that determine healthy ageing. The highly conserved sirtuin deacetylases were shown to regulate life-span in lower organisms. Yet, the role of mammalian sirtuins, SIRT1 to 7, in regulating life-span is currently unclear. Here, we show that in SIRT6 transgenic mice (Sirt6-tg), the males but not the females, have a significant increase in life-span. Gene expression analysis revealed significant differences for male Sirt6-tg in comparison to male wild-type mice. Transgenic males display lower serum IGF-1 levels, increased levels of IGFBP-1 and altered phosphorylation levels of major components of the IGF-1 pathway, a key factor in the regulation of life-span. This study is the first to show regulation of mammalian life-span by a sirtuin family member, and has important therapeutic implications for age-related diseases.
2012-04-01 | E-MTAB-871 | biostudies-arrayexpress
Project description:Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic gluconeogenesis (GNG) capacity in wild type mice. In contrast, aged SIRT6-transgenic mice preserve GNG capacity and glucose homeostasis through an improvement in the utilization of two major GNG precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic GNG gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.
2021-03-11 | PXD021447 | Pride
Project description:wy-14643 activates PPARA to promote beta oxidation. SIRT6 is known to promote beta oxidation. Here we examine the effect of PPARA activation in SIRT6 heterozygote mice.
2019-12-15 | GSE140063 | GEO
Project description:Microarray analysis of liver tissue from WT SIRT6 and conditional knockout of SIRT6 using albumin-Cre (SIRT6Co/Co ;Alb-Cre) at 2 and 8 months of age RNA was extracted from mouse liver tissue at 2 and 8 months of age. RNA from three pairs of WT SIRT6 and SIRT6Co/Co ;Alb-Cre mice was combined and hybridized to Affymetrix mouse gene 1.0 ST arrays.
2010-06-08 | E-GEOD-21965 | biostudies-arrayexpress
Project description:Sirt6 is a multifunctional enzyme that regulates diverse cellular processes such as metabolism, DNA repair, and aging. Overexpressing Sirt6 extends lifespan in mice, but the underlying cellular mechanisms are unclear. Drosophila melanogaster are an excellent model to study genetic regulation of lifespan; however, despite extensive study in mammals, very little is known about Sirt6 function in flies. Here, we characterized the Drosophila ortholog of Sirt6, dSirt6, and examined its role in regulating longevity. dSirt6 is a nuclear and chromatin-associated protein with NAD+-dependent histone deacetylase activity. dSirt6 overexpression in flies produces robust lifespan extension in both sexes, while reducing dSirt6 levels shortens lifespan. dSirt6 OE flies have normal food consumption and fertility, but increased resistance to oxidative stress and reduced protein synthesis rates. Transcriptomic analyses reveal that dSirt6 OE reduces expression of genes involved in ribosome biogenesis, including many dMyc target genes. dSirt6 OE partially rescues many effects of dMyc OE, including increased nuclear size, up-regulation of ribosome biogenesis genes, and lifespan shortening. Lastly, dMyc haploinsufficiency does not convey additional lifespan extension to dSirt6 OE flies, suggesting dSirt6 OE is upstream of dMyc in regulating lifespan. Our results provide new insight into the mechanisms by which Sirt6 overexpression leads to longer lifespan.
2021-12-23 | GSE191320 | GEO
Project description:The SIRT6 Activator MDL-800 Extends Lifespan and Health-span of Mice
| PRJNA604777 | ENA
Project description:Microarray analysis of liver tissue from WT SIRT6 and conditional knockout of SIRT6 using albumin-Cre (SIRT6Co/Co ;Alb-Cre) at 2 and 8 months of age
2010-05-28 | GSE21965 | GEO
Project description:The study found reciprocal regulation between SIRT6 and APC/C. While SIRT6 is ubiquitinated by APC/C and degraded, CDH1, a co-activator of APC/C, is also deacetylated by SIRT6 and degraded.
2021-09-09 | PXD022402 | Pride
Project description: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.
2021-06-18 | GSE178432 | GEO