Age-related changes of gene expression profiles in Drosophila
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA777691 | ENA |
REPOSITORIES: ENA
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Project description:An individual’s gene expression profile changes throughout life. This change in gene expression is shaped by differences in physiological needs and functions between the younger and older organism. Here we report a transcriptomic analysis of Drosophila melanogaster using microarrays. We compared the expression profiles of two-day-old female adult flies with those of 45-day-old flies. We identified 1184 genes with pronounced expression level differences between young and old age groups. Most genes involved in muscle development/maintenance that display different levels of expression with age were downregulated in older flies. Many of these genes contributed to sarcomere formation and function. Several of these genes were functionally related to direct and indirect flight muscles; some of them were exclusively expressed in these muscles. Conversely, several genes involved in apoptosis processes were upregulated in aging flies. Close to half of these genes, such as different caspases, promote cell death, whereas the other half is associated with the inhibition of apoptosis. Several genes that inhibit apoptosis contribute to cell-type maintenance for different cell groups, including neurons, cardiac cells, and salivary gland cells. In addition, several genes involved in resistance to toxic chemicals were upregulated in aging flies, which is consistent with a global upregulation of the defense response system in aging flies. Finally, 232 of the differentially expressed genes had no known functions.
2021-12-10 | GSE187896 | GEO
Project description:Hippocampal Subregion Transcriptomic Profiles Associated with Age-Related Changes in Spatial Pattern Separation
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Project description:Hui2014 - Age-related changes in articular
cartilage
This model is described in the article:
Oxidative changes and
signalling pathways are pivotal in initiating age-related
changes in articular cartilage
Wang Hui1, David A Young1, Andrew D
Rowan1, Xin Xu2, Tim E Cawston1, Carole J Proctor1,3
Annals of the Rheumatic Diseases
Abstract:
Objective: To use a computational approach to investigate
the cellular and extracellular matrix changes that occur with
age in the knee joints of mice. Methods: Knee joints from an
inbred C57/BL1/6 (ICRFa) mouse colony were harvested at
3–30?months of age. Sections were stained with H&E,
Safranin-O, Picro-sirius red and antibodies to matrix
metalloproteinase-13 (MMP-13), nitrotyrosine, LC-3B, Bcl-2, and
cleaved type II collagen used for immunohistochemistry. Based
on this and other data from the literature, a computer
simulation model was built using the Systems Biology Markup
Language using an iterative approach of data analysis and
modelling. Individual parameters were subsequently altered to
assess their effect on the model. Results: A progressive loss
of cartilage matrix occurred with age. Nitrotyrosine, MMP-13
and anaplastic lymphoma kinase (ALK1) staining in cartilage
increased with age with a concomitant decrease in LC-3B and
Bcl-2. Stochastic simulations from the computational model
showed a good agreement with these data, once transforming
growth factor-? signalling via ALK1/ALK5 receptors was
included. Oxidative stress and the interleukin 1 pathway were
identified as key factors in driving the cartilage breakdown
associated with ageing. Conclusions: A progressive loss of
cartilage matrix and cellularity occurs with age. This is
accompanied with increased levels of oxidative stress,
apoptosis and MMP-13 and a decrease in chondrocyte autophagy.
These changes explain the marked predisposition of joints to
develop osteoarthritis with age. Computational modelling
provides useful insights into the underlying mechanisms
involved in age-related changes in musculoskeletal tissues.
This model is hosted on
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BIOMD0000000560.
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2019-09-04 | BIOMD0000000560 | BioModels
Project description:Previous studies of age-related transcriptional changes indicate that cognitive impairments are associated with differentially expressed genes DEGs linked to defined neural systems; however, studies that examine multiple regions of the hippocampus fail to find major links between behavior and transcription in the dentate gyrus DG. The DG is implicated in pattern separation PS and exhibits multiple age-related changes that may affect PS performance. We hypothesize that an age-related decline in PS performance is associated with distinct changes in transcriptional profile, most strongly within the DG compared to other hippocampal subregions. We used a water maze beacon discrimination task to characterize PS in young 5 mo and middle-age 12 mo male F344 rats, followed by a spatial reference memory test. Middle-age rats showed consistent deficits in discriminating two identical beacons compared to young. Reference memory was not different between these two age groups. Interestingly, with increasing spatial overlap between the cues, older animals appeared to compensate for impaired PS performance though greater reliance on spatial reference memory. mRNA sequencing of hippocampal subregions DG, CA1, and CA3 indicated that the DG of middle-age rats expressed more genes correlated with PS performance. In contrast, reliance on a spatial reference memory was associated with differential expression of genes in regions CA1 and CA3. These results indicate that the beacon task is sensitive to PS impairment as early as middle-age, and distinct gene profiles are observed in neural circuits that underlie different strategies used to solve the task.
2020-05-22 | GSE140420 | GEO