Dataset Information

Transcriptome States Reflect Imaging of Aging States.

ABSTRACT: In this study, we describe a morphological biomarker that detects multiple discrete subpopulations (or "age-states") at several chronological ages in a population of nematodes (Caenorhabditis elegans). We determined the frequencies of three healthy adult states and the timing of the transitions between them across the lifespan. We used short-lived and long-lived strains to confirm the general applicability of the state classifier and to monitor state progression. This exploration revealed healthy and unhealthy states, the former being favored in long-lived strains and the latter showing delayed onset. Short-lived strains rapidly transitioned through the putative healthy state. We previously found that age-matched animals in different age-states have distinct transcriptome profiles. We isolated animals at the beginning and end of each identified state and performed microarray analysis (principal component analysis, relative sample to sample distance measurements, and gene set enrichment analysis). In some comparisons, chronologically identical individuals were farther apart than morphologically identical individuals isolated on different days. The age-state biomarker allowed assessment of aging in a novel manner, complementary to chronological age progression. We found hsp70 and some small heat shock protein genes are expressed later in adulthood, consistent with the proteostasis collapse model.

SUBMITTER: Eckley DM

PROVIDER: S-EPMC6001903 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Transcriptome States Reflect Imaging of Aging States.

Eckley D Mark DM Coletta Christopher E CE Orlov Nikita V NV Wilson Mark A MA Iser Wendy W Bastian Paul P Lehrmann Elin E Zhang Yonqing Y Becker Kevin G KG Goldberg Ilya G IG

The journals of gerontology. Series A, Biological sciences and medical sciences 20180601 7

In this study, we describe a morphological biomarker that detects multiple discrete subpopulations (or "age-states") at several chronological ages in a population of nematodes (Caenorhabditis elegans). We determined the frequencies of three healthy adult states and the timing of the transitions between them across the lifespan. We used short-lived and long-lived strains to confirm the general applicability of the state classifier and to monitor state progression. This exploration revealed health ...[more]

PMID: 29216338

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Project description:Age-related cognitive impairments are associated with differentially expressed genes (DEGs) linked to defined neural systems; however, studies examining multiple regions of the hippocampus fail to find links between behavior and transcription in the dentate gyrus (DG). We hypothesized that use of a task requiring intact DG function would emphasize molecular signals in the DG associated with a decline in performance. We used a water maze beacon discrimination task to characterize young and middle-age male F344 rats, followed by a spatial reference memory probe trial test. Middle-age rats showed increased variability in discriminating two identical beacons. Use of an allocentric strategy and formation of a spatial reference memory were not different between age groups; however, older animals compensated for impaired beacon discrimination through greater reliance on spatial reference memory. mRNA sequencing of hippocampal subregions indicated DEGs in the DG of middle-age rats, linked to synaptic function and neurogenesis, correlated with beacon discrimination performance, suggesting that senescence of the DG underlies the impairment. Few genes correlated with spatial memory across age groups, with a greater number in region CA1. Age-related CA1 DEGs, correlated with spatial memory, were linked to regulation of neural activity. These results indicate that the beacon task is sensitive to impairment in middle age, and distinct gene profiles are observed in neural circuits that underlie beacon discrimination performance and allocentric memory. The use of different strategies in older animals and associated transcriptional profiles could provide an animal model for examining cognitive reserve and neural compensation of aging.SIGNIFICANCE STATEMENT Hippocampal subregions are thought to differentially contribute to memory. We took advantage of age-related variability in performance on a water maze beacon task and next-generation sequencing to test the hypothesis that aging of the dentate gyrus is linked to impaired beacon discrimination and compensatory use of allocentric memory. The dentate gyrus expressed synaptic function and neurogenesis genes correlated with beacon discrimination in middle-age animals. Spatial reference memory was associated with CA1 transcriptional correlates linked to regulation of neural activity and use of an allocentric strategy. This is the first study examining transcriptomes of multiple hippocampal subregions to link age-related impairments associated with discrimination of feature overlap and alternate response strategies to gene expression in specific hippocampal subregions.

Dataset Information

Transcriptome States Reflect Imaging of Aging States.

Publications

Transcriptome States Reflect Imaging of Aging States.

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