DNA Methylation of primary human fibroblasts across replicative lifespan in normal and hyperglycemic conditions
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ABSTRACT:
PROVIDER: PRJNA543113 | ENA |
REPOSITORIES: ENA
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Project description:Genome wide DNA methylation profiling of normal (5.5mM) and high (25mM) glucose samples from primary human fibroblasts across the cellular lifespan. The Illumina Infinium EPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 866,836 CpGs. Samples included 12 normal glucose time points and 14 high glucose time points, as well as, 6 technical replicates of normal glucose timepoint at 34.8 days. Methylation data was used to estimate the rate of aging occuring across replicative lifespan using several DNA methylation based Aging Clocks. Other analysis include comparing the overlap of age-related CpGs in vitro to in vivo, and describing the diverse kinetics of methylation sites across cellular lifespan.
2019-05-16 | GSE131280 | GEO
Project description:Aneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality-control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age-associated phenotypes. These are all CGH arrays comparing DNA content between the indicated strain of interest and a wt control.
2015-12-04 | E-GEOD-75623 | biostudies-arrayexpress
Project description:Aneuploidy and aging are correlated; however, a causal link between these two phenomena has remained elusive. Here we show that yeast disomic for a single native yeast chromosome generally have a decreased replicative lifespan. In addition, the extent of this lifespan deficit correlates with the size of the extra chromosome. We identified a mutation in BUL1 that rescues both the lifespan deficit and a protein trafficking defect in yeast disomic for chromosome 5. Bul1 is an E4 ubiquitin ligase adaptor involved in a protein quality-control pathway that targets membrane proteins for endocytosis and destruction in the lysosomal vacuole thereby maintaining protein homeostasis. Concurrent suppression of the aging and trafficking phenotypes suggests that disrupted membrane protein homeostasis in aneuploid yeast may contribute to their accelerated aging. The data reported here demonstrate that aneuploidy can impair protein homeostasis, shorten lifespan, and may contribute to age-associated phenotypes.
2015-12-04 | GSE75623 | GEO
Project description:Application of microfluidic platforms facilitated high-precision measurements of yeast replicative lifespan (RLS); however, comparative quantification of lifespan across strain libraries has been missing. Here we microfluidically measured RLS of 307 yeast strains, each deleted for a single gene. Despite previous reports of extended lifespan in these strains, we found that 56% of them did not actually live longer than the wild-type; while the remaining 44% showed extended lifespans, the degree of extension was often different from what was previously reported. Deletion of SIS2 gene led to the largest RLS increase observed. Sis2 regulated yeast lifespan in a dose-dependent manner, implying a role for the coenzyme A biosynthesis pathway in lifespan regulation. Introduction of the human PPCDC gene in the sis2Δ background neutralized the lifespan extension. RNA-seq experiments revealed transcriptional increases in cell-cycle machinery components in sis2Δ background. High-precision lifespan measurement will be essential to elucidate the gene network governing lifespan.
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Project description:In this study we perform ATAC-seq of budding yeast strains with variable copy number of the rRNA genes (rDNA CN). We aim to better understand the relationship between DNA accessibility and replicative lifespan in strains with variable rDNA CN.
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Project description:Sis2 regulates yeast replicative lifespan in a dose-dependent manner
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Project description:Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan. Phylogenetic analyses pointed to genes and environmental factors that strongly interact to modulate the observed aging patterns. We then identified genetic networks causally associated with natural variation in replicative lifespan across wild yeast isolates, as well as genes, metabolites and pathways, many of which have never been associated with yeast lifespan in laboratory settings. In addition, a combined analysis of lifespan-associated metabolic and transcriptomic changes revealed unique adaptations to interconnected amino acid biosynthesis, glutamate metabolism and mitochondrial function in long-lived strains. Overall, our multi-omic and lifespan analyses across diverse isolates of the same species shows how gene-environment interactions shape cellular processes involved in phenotypic variation such as lifespan.
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Project description:The involvement of protein chaperones in aging is intriguing and their potential contribution has, so far, been attributed solely to their central role in proteostasis. Here we show that four protein chaperones from different cellular compartments extend replicative lifespan (RLS) in budding yeast by a common mechanism akin to caloric restriction. The RLS extension relies on the increased direct activation of Snf1 kinase by Hsp90, thereby bypassing the signal on the environmental glucose level. The chaperone-related RLS extension is accompanied by the uncoupling of the respiratory chain. A genomic approach confirmed the repression of glycolysis and cytoplasmic translation, and contrary, activation of gluconeogenesis and fatty acid oxidation. Our results set a novel paradigm for the role of protein chaperones: by modulation of the chaperone expression level one can affect metabolic features such as glucose sensing, fatty acid consumption, respiration rate, and, consequently, modify lifespan. We expect the described mechanism to open new avenues for research in aging and age-related diseases.
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Project description:A crucial step towards understanding the mechanisms underlying aging is to obtain an integrated account of the molecular changes during aging. To address this, we mapped the yeast (S. cerevisiae) transcriptome during the replicative lifespan of budding yeast using novel culture and computational methods.
2015-10-06 | E-MTAB-3605 | biostudies-arrayexpress