The Longevity Factor Spermidine is Part of a Highly Heritable Complex Erythrocyte Phenotype Associated With Longevity
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Elite
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Thomas Raife
PROVIDER: MSV000093812 | MassIVE | Wed Jan 10 12:35:00 GMT 2024
REPOSITORIES: MassIVE
Similar Datasets
Project description:To investigate the molecular and physiological functions of SWAP1 in light signaling. We show that SWAP1 modulates global gene expression and alternative splicing both under dark and red light treated conditions
2022-11-09 | GSE214299 | GEO
Project description:ABSTRACT Primary human distal lung/parenchymal fibroblasts (DLF) exhibit a different phenotype from airway fibroblasts (AF), including the expression of high levels of a-smooth muscle actin (a-SMA). The scope of the differences and the mechanisms driving them are unknown. To determine whether distinct fibroblast characteristics and function based on lung region are predicted by a broad range of genomic differences in AF vs DLF. Matched human fibroblast pairs isolated from proximal and distal lung in 18 asthmatic and 4 normal subjects were studied. Microarray analysis was performed on 12 matched fibroblast pairs (8 asthmatic and 4 normal subjects) and validated by quantitative real-time PCR (qRT-PCR). The functional impact of these molecular differences on AF and DLF was then revealed using computational approaches. Microarray data demonstrated 474 transcripts upregulated in AF, and 611 transcripts upregulated in DLF, when the asthmatic and normal fibroblasts were combined for all the analysis. Further gene ontology (GO) and network analysis identified distinct pathway activation patterns between AF and DLF, including identification of the SMAD3 and MAPK8 signaling pathways. These results demonstrated that marked molecular and functional differences exist between these two lung regional fibroblast populations. These striking differences identify multiple potential mechanisms by which AF and DLF differ in their responses to injury, regeneration and remodeling in the lungs. In order to better identify the underlying molecular differences between AF and DLF, microarray analysis was performed on 12 different matched pairs of fibroblasts (4 pairs from normal subjects and 8 pairs from asthmatics).
2011-07-21 | E-GEOD-27335 | biostudies-arrayexpress
Project description:We sequenced mRNA from blastoderm embryos of Drosophila melanogaster, Drosophila yakuba, Drosophila pseudoobscura and Drosophila virilis. Two samples contain pooled mRNA from several species, and the remaining 24 samples contain mRNA from a single species. Methods: Retinal mRNA profiles of Blastoderm embryos
2013-09-12 | GSE50766 | GEO
Project description:To better characterize how variation in regulatory sequences drives divergence in gene expression, we undertook a systematic study of transcription factor binding and gene expression in blastoderm embryos of four species, which sample much of the diversity in the 40 million-year old genus Drosophila: D. melanogaster, D. yakuba, D. pseudoobscura and D. virilis. We compared gene expression, measured by mRNA-seq, to the genome-wide binding, measured by ChIP-seq, of four transcription factors involved in early anterior-posterior patterning. We found that mRNA levels are much better conserved than individual transcription factor binding events, and that changes in a gene’s expression were poorly explained by changes in adjacent transcription factor binding. However highly bound sites, sites in regions bound by multiple factors and sites near genes are conserved more frequently than other binding, suggesting that a considerable amount of transcription factor binding is weakly or non-functional and not subject to purifying selection
2013-09-12 | GSE50771 | GEO
Project description:Analysis of gene expression in injured primary DRG with or without camptothecin (CPT) treatment after sciatic nerve crushing may help us identify critical molecular pathways related to axon regeneration. We performed RNA-sequencing of (i) Naive primary DRG tissues without injury, (ii) Primary DRG tissues with vehicle treatment different time-points (18, 24, 36 hours) after sciatic nerve injury, and (iii) Primary DRG tissues with camptothecin treatment different time-points (18, 24, 36 hours) after sciatic nerve injury.
2020-07-24 | GSE113672 | GEO
Project description:Mediator of ErbB2-driven cell Motility 1 (MEMO1) is an intracellular redox protein that integrates growth factors signaling with the intracellular redox state. We have previously reported that mice lacking Memo1 displayed higher plasma calcium levels and other alterations of mineral metabolism, but the underlying mechanism was unresolved and the bone phenotype was not described. Here, we show that Cre/lox-mediated MEMO1 deletion in the whole body of C57Bl/6 mice (Memo cKO) leads to severely altered trabecular bone and lower mineralization, with preserved osteoblast and osteoclast number and activity, but altered osteoblast response to epidermal growth factor (EGF) and FGF2. More strikingly, Memo cKO mice display decreased alkaline phosphatase (ALP) activity in serum and in bone, while ALPL expression level is unchanged. Bone intracellular redox state is significantly altered in Memo cKO mice and we inferred that ALP dimerization was reduced in Memo cKO mice. Indeed, despite similar ALP oxidation, we found increased ALP sensitivity to detergent in Memo cKO bone leading to lower ALP dimerization capability. Thus, we report a severe bone phenotype and dysfunctional bone ALP with local alteration of the redox state in Memo cKO mice that partially mimics hypophosphatasia, independent of ALPL mutations. These findings reveal Memo as a key player in bone homeostasis and underline a role of bone redox state in controlling ALP activity.
| S-EPMC6054794 | biostudies-literature
Project description:264 DDA files corresponding to 36 mouse organs; PulseDIA data profiling of 41 male mouse organs and nine pairs of organs
2022-08-25 | PXD036255 | iProX
Project description:PPARGC1A is a transcriptional coactivator that binds to and coactivates a variety of transcription factors (TFs) to regulate the expression of target genes. PPARGC1A plays a pivotal role in regulating energy metabolism and has been implicated in several human diseases, most notably type II diabetes. Previous studies have focused on the interplay between PPARGC1A and individual TFs, but little is known about how PPARGC1A combines with all of its partners across the genome to regulate transcriptional dynamics. In this study, we describe a core PPARGC1A transcriptional regulatory network operating in HepG2 cells treated with forskolin. We first mapped the genome-wide binding sites of PPARGC1A using chromatin-IP followed by high-throughput sequencing (ChIP-seq) and uncovered overrepresented DNA sequence motifs corresponding to known and novel PPARGC1A network partners. We then profiled six of these site-specific TF partners using ChIP-seq and examined their network connectivity and combinatorial binding patterns with PPARGC1A. Our analysis revealed extensive overlap of targets including a novel link between PPARGC1A and HSF1, a TF regulating the conserved heat shock response pathway that is misregulated in diabetes. Importantly, we found that different combinations of TFs bound to distinct functional sets of genes, thereby helping to reveal the combinatorial regulatory code for metabolic and other cellular processes. In addition, the different TFs often bound near the promoters and coding regions of each other's genes suggesting an intricate network of interdependent regulation. Overall, our study provides an important framework for understanding the systems-level control of metabolic gene expression in humans.
| S-EPMC3431484 | biostudies-literature
Project description:This data set represents a reanalysis of human blood plasma samples measured by SWATH-MS of 36 pairs of monozygotic and 22 pairs of dizygotic twins that were sampled at two longitudinal time points (Liu et al., 2015, PMID:25652787). The data were used to determine the overall quantitative variability of 4322 peptidoforms in the sample cohort and to assign the measured variability to heritability, environmental or longitudinal effects.
2017-06-06 | PXD004574 | Pride
Project description:Longevity was influenced by many complex diseases and traits. However, the relationships between human longevity and genetic risks of complex diseases were not broadly studied. Here, we constructed polygenic risk scores (PRSs) for 225 complex diseases/traits and evaluated their relationships with human longevity in a cohort with 2178 centenarians and 2299 middle-aged individuals. Lower genetic risks of stroke and hypotension were observed in centenarians, while higher genetic risks of schizophrenia (SCZ) and type 2 diabetes (T2D) were detected in long-lived individuals. We further stratified PRSs into cell-type groups and significance-level groups. The results showed that the immune component of SCZ genetic risk was positively linked to longevity, and the renal component of T2D genetic risk was the most deleterious. Additionally, SNPs with very small p-values (p ≤ 1x10-5 ) for SCZ and T2D were negatively correlated with longevity. While for the less significant SNPs (1x10-5 < p ≤ 0.05), their effects on disease and longevity were positively correlated. Overall, we identified genetically informed positive and negative factors for human longevity, gained more insights on the accumulation of disease risk alleles during evolution, and provided evidence for the theory of genetic trade-offs between complex diseases and longevity.
| S-EPMC9282840 | biostudies-literature