Project description:Wildtype mice at either 3 or 12 months old were subjected to intrahippocampal injection with sarkosyl insoluble brain extracts from either human control or Alzheimer's disease brain. Mice were incubated for 1, 3 or 5 months and then sacrificed. The hippocampus from one hemisphere was used to extract total RNA that was then subjected to polyA-selection and whole transcriptome sequencing. 3 and 12 month old animals were processed in seperate batches and comparisons between control and Alzheimer's disease injected animals from each timepoint were conducted
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.
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Project description:Aging is associated with major nuclear changes affecting genomic integrity and gene expression. Here we compare the gene expression profiles in the neocortex of young (5 months old) and old (30 months old) B6xC3 F1 mice. In a related study, we compare genes that change expression with age to SIRT1 associated genes identified by ChIP on chip (NimbleGen) and find a significant overlap, indicating that SIRT1 target genes are preferentially deregulated with age. Keywords: gene expression comparison, age-comparison
Project description:Age-related hearing loss is a multifactorial and progressive process, which negatively impacts quality of life in many senior adults as the number one chronic neurodegenerative condition. This study was done to examine gene expression changes occurring in mouse auditory nerve and cochlear lateral wall tissues that may contribute to age-related hearing loss. In addition to conducting general differential expression analysis, a focused analysis of genes linked to neural cells was done.