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Status |
Public on Aug 04, 2017 |
Title |
Caloric restriction impacts plasma microRNAs in rhesus monkeys |
Organism |
Macaca mulatta |
Experiment type |
Non-coding RNA profiling by high throughput sequencing
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Summary |
Caloric restriction (CR) is one of the most robust interventions shown to delay aging in diverse species, including rhesus monkeys (Macaca mulatta). Identification of factors involved in CR brings a promise of translatability to human health and aging. Here, we show that CR induced a profound change in abundance of circulating microRNAs (miRNAs) linked to growth and insulin signaling pathway, suggesting that miRNAs are involved in CR’s mechanisms of action in primates. Deep sequencing of plasma RNA extracts enriched for short species revealed a total of 243 unique species of miRNAs including 47 novel species. Approxi- mately 70% of the plasma miRNAs detected were conserved between rhesus monkeys and humans. CR induced or repressed 24 known and 10 novel miRNA species. Regression analysis revealed correlations between bodyweight, adiposity, and insulin sensitivity for 10 of the CR-regulated known miRNAs. Sequence alignment and target identification for these 10 miRNAs identify a role in signaling downstream of the insulin receptor. The highly abundant miR-125a-5p correlated positively with adiposity and negatively with insulin sensitivity and was negatively regulated by CR. Putative target pathways of CR- associated miRNAs were highly enriched for growth and insulin signaling that have previously been implicated in delayed aging. Clustering analysis further pointed to CR-induced miRNA regula- tion of ribosomal, mitochondrial, and spliceosomal pathways. These data are consistent with a model where CR recruits miRNA- based homeostatic mechanisms to coordinate a program of delayed aging.
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Overall design |
Serum miRNA profile of rhesus monkeys on calorie restriction or control diet was analyzed. For each group 5 samples were processed. Serum was collected, total RNA was isolated using miRNeasy kit (Qiagen). One fourth (5 μL) of the RNA isolated from each plasma sample was used to construct sequencing libraries with the Illumina TruSeq Small RNA Sample Prep Kit (Illumina). The libraries were pooled in equimolar amounts and submitted to sequencing.
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Contributor(s) |
Schneider A, Dhahbi JM, Atamna H, Clark JP, Colman RJ, Anderson RM |
Citation(s) |
28677323 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 AG040178 |
Caloric Restriction and Aging in Rhesus Monkeys |
UNIVERSITY OF WISCONSIN MADISON |
ROZALYN M ANDERSON |
R56 AG047358 |
Reproductive Hormones in Skeletal Muscle Aging in Rhesus Monkeys |
UNIVERSITY OF WISCONSIN MADISON |
ROZALYN M ANDERSON |
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BioProject |
PRJNA392879 |
Submission date |
Aug 03, 2017 |
Last update date |
May 15, 2019 |
Contact name |
Augusto Schneider |
Organization name |
University of Central Florida
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Department |
Burnett School of Biomedical Sciences
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Street address |
6900 Lake Nona Blvd
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City |
Orlando |
State/province |
FL |
ZIP/Postal code |
32827 |
Country |
USA |
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Platforms (1) |
GPL14954 |
Illumina HiSeq 2000 (Macaca mulatta) |
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Samples (10)
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Relations |
SRA |
SRP113659 |