Fetal origin of sex-bias brain aging [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE215138 | GEO | 2022/10/12
REPOSITORIES: GEO
Similar Datasets
Project description:DNA methylation plays crucial roles during fetal development as well as aging. Whether the aging of the brain is programmed at the fetal stage remains untested. To test this hypothesis, mouse epigenetic clock (epiclock) was profiled in fetal (gestation day 15), postnatal (day 5), and aging (week 70) brain of male and female C57BL/6J inbred mice. Data analysis showed that on week 70, the female brain was epigenetically younger than the male brain. Predictive modeling by neural network identified specific methylations in the brain at the developing stages that were predictive of epigenetic state of the brain during aging. Transcriptomic analysis showed coordinated changes in the expression of epiclock genes in the fetal brain relative to the placenta. Whole-genome bisulfite sequencing identified sites that were methylated both in the placenta and fetal brain in a sex-specific manner. Epiclock genes and genes associated with specific signaling pathways, primarily the gonadotropin-releasing hormone receptor (GnRHR) pathway, were associated with the sex-bias methylations in the placenta as well as the fetal brain. Transcriptional crosstalk among the epiclock and GnRHR pathway genes was evident in the placenta that was maintained in the brain during development as well as aging. Collectively, these findings suggest that sex differences in the aging of the brain are of fetal origin and epigenetically linked to the placenta.
2022-08-22 | GSE157553 | GEO
Project description:The naked mole-rat (NMR) is an exceptionally long-lived rodent that does not show increased mortality with age, uniquely defining NMR as a demographically non-aging mammal. Here, we performed bisulfite sequencing on over one hundred NMR blood samples differing in age, assessing more than 3 million common CpG sites. We observed an information loss of the NMR methylome during aging suggesting that NMR ages. Unsupervised clustering based on the 758 CpG sites whose methylation level strongly correlate with age suggests an age-related shift of the NMR methylome. We also developed an epigenetic aging clock that accurately predicts the NMR age spread across the genome. Based on the clock, NMRs age much slower than mice and much faster than humans, consistent with their known maximum lifespans. We further found that patterns of age-related methylation changes of aging clock sites in Tert and Prpf19 showed differences between NMRs and mice. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species.
2021-12-19 | GSE179039 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24992: Drosophila brain microRNA expression with age: miRNA profiling GSE25007: Drosophila brain gene expression with age: mRNA profiling GSE25008: Drosophila brain gene expression between wildtype and miR-34 null flies Refer to individual Series. Aging is the most prominent risk factor for human neurodegenerative disease, but underlying mechanisms that connect two processes are less well characterized. With age, the brain undergoes functional decline and perhaps degeneration. Such decline may not just contribute to normal aging, but also enhance susceptibility to and progression of age-related neurodegenerative diseases. Therefore, defining intrinsic factors and pathways that underline the normal integrity of the adult nervous system may lead to insights that potentially link aging and neurodegeneration. Here, we report a highly conserved microRNA (miRNA), miR-34, as a modulator of aging and neurodegeneration. Using Drosophila, we show that fly miR-34 expression is brain-enriched and strikingly upregulated with age. Functional studies reveal that, whereas animals without miR-34 are normal as young adults, upon aging, they gradually show late-onset deficits characteristic of accelerated brain aging; these include a transcriptional signature of aged animals, coupled with rapid functional decline, loss of brain integrity, followed by a catastrophic decline in adult viability. Moreover, upregulation of miR-34 protects against neurodegeneration induced by pathogenic human polyglutamine (polyQ) disease protein. We next reveal a dramatic effect of miR-34 to silence the Eip74EF gene of steroid hormone pathways in the adult, which is crucial to maintain the normal aging. Collectively, these data define a miR-34-mediated mechanism that specifically affects long-term integrity of the adult nervous system. miR-34 function in Drosophila may thus present a link that functionally connects aging and neurodegeneration. Our studies implicate essential roles of miRNA- dependent pathways in maintenance of the adult brain, disease pathogenesis and healthy aging.
2011-12-23 | E-GEOD-25009 | biostudies-arrayexpress
Project description:The establishment of highly accurate aging clocks based on DNA methylation highlighted the strong link between epigenetic alterations and aging. However, connecting methylation clocks to physiological changes is not straightforward. Transcriptomics and proteomics clocks on the other hand are directly connected to cellular function, yet they do not allow us to understand underlying epigenetic mechanisms. We hypothesize that chromatin accessibility, a readout that integrates many epigenetic mechanisms, may bridge epigenetic changes with their downstream effects in aging. To demonstrate that chromatin accessibility can predict age, we generated chromatin accessibility profiles from peripheral blood mononuclear cells (PBMCs) of 157 human donors, aged 20 to 74 and used them to construct a novel aging clock. Our clock predicted age with a root mean squared error of 7.69 years, a median absolute error of 5.69 years and a correlation of 0.83. Moreover, by comparing our chromatin accessibility data to matched transcriptomic profiles, we show that the genomic sites selected by our clock drive changes in transcription during aging. This chromatin accessibility clock could therefore be used to better understand the mechanisms driving the process of aging and evaluate anti-aging interventions.
2022-12-01 | GSE193141 | GEO
Project description:The establishment of highly accurate aging clocks based on DNA methylation highlighted the strong link between epigenetic alterations and aging. However, connecting methylation clocks to physiological changes is not straightforward. Transcriptomics and proteomics clocks on the other hand are directly connected to cellular function, yet they do not allow us to understand underlying epigenetic mechanisms. We hypothesize that chromatin accessibility, a readout that integrates many epigenetic mechanisms, may bridge epigenetic changes with their downstream effects in aging. To demonstrate that chromatin accessibility can predict age, we generated chromatin accessibility profiles from peripheral blood mononuclear cells (PBMCs) of 157 human donors, aged 20 to 74 and used them to construct a novel aging clock. Our clock predicted age with a root mean squared error of 7.69 years, a median absolute error of 5.69 years and a correlation of 0.83. Moreover, by comparing our chromatin accessibility data to matched transcriptomic profiles, we show that the genomic sites selected by our clock drive changes in transcription during aging. This chromatin accessibility clock could therefore be used to better understand the mechanisms driving the process of aging and evaluate anti-aging interventions.
2022-12-01 | GSE193140 | GEO
Project description:Sirtuin 1 (SIRT1) is involved in both aging and circadian-clock regulation, yet the link between the two processes in relation to SIRT1 function is not clear. Using Sirt1-deficient mice, we found that Sirt1 and Period 2 (Per2) constitute a reciprocal negative regulation loop that plays important roles in modulating hepatic circadian rhythmicity and aging. Sirt1-deficient mice exhibited profound premature aging and enhanced acetylation of histone H4 on lysine16 (H4K16) in the promoter of Per2, the latter of which leads to its overexpression; in turn, Per2 suppresses Sirt1 transcription through binding to the Sirt1 promoter at the Clock/Bmal1 site. This negative reciprocal relationship between SIRT1 and PER2 was also observed in human hepatocytes. We further demonstrated that the absence of Sirt1 or the ectopic overexpression of Per2 in the liver resulted in a dysregulated pace of the circadian rhythm. The similar circadian rhythm was also observed in aged wild type mice. The interplay between Sirt1 and Per2 modulates aging gene expression and circadian-clock maintenance. To investigate hepatic SIRT1-dependent aging related genes, livers from wild type mice at 3 months (young), 12 months (middle age), and 19 months (old) of age, as well as Sirt1-deficient mice at 3 months of age were snap frozen and subject to RNA isolation and microarray analysis.
2016-08-08 | E-GEOD-54436 | biostudies-arrayexpress
Project description:Dynamic remodeling in architecture and function of mammalian brain, especially in primate, rely on a precisely orchestrated molecular and cellular regulation at distinct levels. Here, we applied comprehensive RNA-seq and CAGE-Seq analysis to characterize dynamics of lncRNA expression in Rhesus macaque brain across postnatal development and aging. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age and sex specificities respectively. Highly spatiotemporal- and sex-specific dynamic changes in lncRNA but mRNA expression and the negative correlation between lncRNAs and mRNAs, functionally associate with brain development and aging, especially in the neocortex. Together with in situ hybridization (ISH) and quantitative real time-PCR (qRT-PCR) data, our findings provide an initial insight into spatial-, age- and sex-related dynamics of lncRNA expression during postnatal brain development and aging in macaque, implying that high dynamics of lncRNA expression might represent a previously unappreciated regulatory system in shaping brain architecture and function.
2017-07-06 | GSE85377 | GEO
Project description:Dynamic remodeling in architecture and function of mammalian brain, especially in primate, rely on a precisely orchestrated molecular and cellular regulation at distinct levels. Here, we applied comprehensive RNA-seq and CAGE-Seq analysis to characterize dynamics of lncRNA expression in Rhesus macaque brain across postnatal development and aging. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age and sex specificities respectively. Highly spatiotemporal- and sex-specific dynamic changes in lncRNA but mRNA expression and the negative correlation between lncRNAs and mRNAs, functionally associate with brain development and aging, especially in the neocortex. Together with in situ hybridization (ISH) and quantitative real time-PCR (qRT-PCR) data, our findings provide an initial insight into spatial-, age- and sex-related dynamics of lncRNA expression during postnatal brain development and aging in macaque, implying that high dynamics of lncRNA expression might represent a previously unappreciated regulatory system in shaping brain architecture and function.
2017-07-06 | GSE87176 | GEO
Project description:MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression post-transcriptionally. Work in Caenorhabditis elegans has shown that specific miRNAs function in lifespan regulation and in a variety of age-associated pathways, but the roles of miRNAs in the aging of vertebrates are not well understood. We examined the expression of small RNAs in whole brains of young and old mice by deep sequencing and report here on the expression of 233 known miRNAs and identification of 41 novel miRNAs. Of these miRNAs, 75 known and 18 novel miRNAs exhibit greater than 2.0-fold expression changes. The majority of expressed miRNAs in our study decline in relative abundance in the aged brain, in agreement with trends observed in other miRNA studies in aging tissues and organisms. Target prediction analysis suggests that many of our novel aging-associated miRNAs target genes in the insulin signaling pathway, a central node of aging-associated genetic networks. These novel miRNAs may thereby regulate aging-related functions in the brain. Since mouse miRNAs are conserved in humans, the aging-affected brain miRNAs we report here may represent novel regulatory genes that function during aging in the human brain. 2 samples examined: Mouse brain from two young (5 months) and two old animals (24-25 months).
2012-05-31 | E-GEOD-34393 | biostudies-arrayexpress
Project description:Aging is accompanied by the functional decline of all tissues, but it is still largely unknown how aging impacts different tissues in a cell type-specific manner. Here, we present the Aging Fly Cell Atlas (AFCA) that includes single-nucleus transcriptomes of the entire Drosophila head and body from both males and females at four different ages. We characterize 162 distinct cell types and present an in-depth analysis of cell type-specific aging features, including changes of cell composition, gene expression, number of expressed genes, transcriptome noise, and cell identity. By combining all aging features, including aging clock models predicting a cell’s age, we find cell-type specific aging patterns. Adipose tissues showed the highest aging score, followed by two cell types from the reproductive system. This transcriptomic atlas provides a valuable resource for the community to study fundamental principles of aging in complex organisms.
2022-12-06 | GSE218661 | GEO