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Status |
Public on Jul 14, 2015 |
Title |
Calorie restriction suppresses age-dependent hippocampal transcriptional signatures. |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging.
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Overall design |
Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.
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Contributor(s) |
Schafer MJ, Dolgalev I, Alldred MJ, Heguy A, Ginsberg SD |
Citation(s) |
26221964 |
Submission date |
Jun 17, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Stephen D Ginsberg |
E-mail(s) |
ginsberg@nki.rfmh.org
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Organization name |
Nathan Kline Institute
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Department |
Center for Dementia Research
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Street address |
140 Old Orangeburg Road
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City |
Orangeburg |
State/province |
NY |
ZIP/Postal code |
10962 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (22)
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Relations |
BioProject |
PRJNA287259 |
SRA |
SRP059596 |
Supplementary file |
Size |
Download |
File type/resource |
GSE69952_fpkm-matrix.csv.gz |
1.6 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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