SIRT6 is a key regulator of mitochondrial function in the brain
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA912711 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22752462.fastq.gz | Fastqsanger.gz | |||
| SRR22752463.fastq.gz | Fastqsanger.gz | |||
| SRR22752464.fastq.gz | Fastqsanger.gz | |||
| SRR22752465.fastq.gz | Fastqsanger.gz | |||
| SRR22752466.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description: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. Unexpectedly, 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 4 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.
2023-02-03 | GSE221077 | GEO
Project description: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.
| S-EPMC9849342 | biostudies-literature
Project description:SIRT6 has been implicated in anti-aging at the organismal level; however, its role in pancreatic beta cell aging is unclear. This study investigated the role of SIRT6 in pancreatic beta cell aging using conditional SIRT6 transgenic overexpression mice at 10 and 16 months of age. Our data show that SIRT6 has a strong protective function against aging-associated oxidative stress, DNA damage, and multiple forms of cell death.
2025-08-23 | GSE287696 | GEO
Project description:SIRT6 Is a Key Regulator of Pancreatic β-Cell Survival and Function During Aging
| PRJNA1214259 | ENA
Project description:Telomere length is important for the maintaining the individual health of a species. However, recent studies have indicated that the telomere length of somatic cells can be drastically decreased in the offspring receiving in vitro fertilization (IVF) therapy, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report for the first time that NAD+ levels are significantly lower in blastocysts cultured in vitro than that in blastocysts developed in vivo, leading to impaired Sirt6 function, further triggering telomere shortening of the inner cell mass and possibly affecting newborn offspring. This phenotype could be effectively mitigated by supplementation with NMN, a precursor of NAD+, during in vitro culture.While it could not be achieved in Sirt6 conditional knockout embryos. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.
2025-07-07 | GSE280684 | GEO
Project description:NAD+-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos
| PRJNA1179958 | ENA
Project description:Telomere length (TL) is important for the maintaining the individual health of a species. However, recent studies have indicated that blastocyst culture may increase the risk of telomere shortening in the offspring of those undergoing in vitro fertilization (IVF) treatment, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD+-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report for the first time that NAD+ levels are significantly lower in blastocysts cultured in vitro than that in blastocysts developed in vivo, leading to impaired Sirt6 function, further triggering telomere shortening of the inner cell mass and possibly affecting newborn offspring. This phenotype could be effectively mitigated by supplementation with nicotinamide mononucleotide (NMN), a precursor of NAD+, during in vitro culture, while it could not be achieved in Sirt6 conditional knockout embryos. Furthermore, mtROS accumulation and epigenetic modifications may also play an important role in this process. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.
2025-07-07 | GSE299048 | GEO
Project description:Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1 and IGF2BP3. This epigenetic program defines a distinct subset representing 30-40% of human PDAC, characterized by poor prognosis and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor, and uncover the Lin28b pathway as a potential therapeutic target in a molecularlydefined PDAC subset. ChIP-Seq experiments to examine H3K56ac histone modifications in murine PDAC cells that are Sirt6 wild type (WT), Sirt6 knock-out (KO), and Sirt6 KO cells engineered to express Sirt6 WT (Sirt6 KO + Sirt6 WT Restored).
2016-04-01 | E-GEOD-79503 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE13206: Human shSIRT6 TNF-alpha timecourse GSE13207: Mouse Sirt6-/- TNF-alpha timecourse GSE13208: Mouse Sirt6-/- tissues GSE13209: Mouse Sirt6-/- RelA+/- tissues Refer to individual Series
2010-06-24 | E-GEOD-13272 | biostudies-arrayexpress
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