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Blood RNA expression profiles undergo major changes during the seventh decade.

ABSTRACT: Genome-wide alterations in RNA expression profiles are age-associated. Yet the rate and temporal pattern of those alterations are poorly understood. We investigated temporal changes in RNA expression profiles in blood from population-based studies using a quadratic regression model. Comparative analysis between two independent studies was carried out after sample-weighting that downsized differences in sample distribution over age between the datasets. We show that age-associated expression profiles are clustered into two major inclinations and transcriptional alternations occur predominantly from the seventh decade onwards. The age-associated genes in blood are enriched in functional groups of the translational machinery and the immune system. The results are highly consistent between the two population-based studies indicating that our analysis overcomes potential confounders in population-based studies. We suggest that the critical age when major transcriptional alterations occur could help understanding aging and disease risk during adulthood.

SUBMITTER: Gheorghe M

PROVIDER: S-EPMC5342083 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Blood RNA expression profiles undergo major changes during the seventh decade.

Gheorghe Marius M Schurmann Claudia C Peters Marjolein J MJ Uitterlinden André G AG Hofman Albert A Biffar Reiner R Homuth Georg G Völker Uwe U van Meurs Joyce B J JB Raz Vered V

Oncotarget 20161101 44

Genome-wide alterations in RNA expression profiles are age-associated. Yet the rate and temporal pattern of those alterations are poorly understood. We investigated temporal changes in RNA expression profiles in blood from population-based studies using a quadratic regression model. Comparative analysis between two independent studies was carried out after sample-weighting that downsized differences in sample distribution over age between the datasets. We show that age-associated expression prof ...[more]

PMID: 27655681

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Project description:ObjectiveOsteoarthritis (OA) is characterized by the chronic and progressive deterioration of articular cartilage. Chondrocyte senescence could lead to a shift in the balance between extracellular matrix (ECM) component synthesis and degradation. Small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), P-element-induced wimpy testis-(PIWI-) interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), and repeat-associated siRNAs (rasiRNAs), are a class of important epigenetic molecules. We aimed to gain insights into the changes and roles of sncRNA in chondrocyte senescence.DesignHealthy mouse postnatal chondrocytes were isolated, and a replicative aging model was constructed. We used small RNA sequencing (small RNA-seq) to generate extensive small RNA data. We identified differentially expressed sncRNAs and performed tissue-specific analysis using real-time quantitative polymerase chain reaction (qRT-PCR). β-galactosidase staining was used to detect chondrocyte senescence. The results showed that the expression profiles of sncRNA in passage 5 chondrocytes were significantly different from those in passage 0 chondrocytes. The expression of sncRNA was tissue specific. We found that 40 miRNAs were upregulated and 70 miRNAs were downregulated during chondrocyte senescence, and that miR-132-5p expression inhibition prevented chondrocyte senescence. We found that 8 piRNAs were upregulated and 17 piRNAs were downregulated during chondrocyte senescence, and that piRNA piR_025576 overexpression delayed chondrocyte senescence. We found that 24 snoRNAs were upregulated and 28 snoRNAs were downregulated during chondrocyte senescence, and that snoRNA ENSMUSG00000087935 overexpression delayed chondrocyte senescence. We found that 5 snRNAs were upregulated and 6 snRNAs were downregulated during chondrocyte senescence, and that snRNA ENSMUSG00000064682 overexpression delayed chondrocyte senescence. We found that 1 rasiRNA was upregulated and 4 rasiRNAs were downregulated during chondrocyte senescence.ConclusionsThese findings might provide novel insights into OA pathogenesis and contribute to the development of candidates for targeted therapeutics in OA.

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Blood RNA expression profiles undergo major changes during the seventh decade.

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Blood RNA expression profiles undergo major changes during the seventh decade.

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