Dataset Information

Age-related micro-RNA abundance in individual C. elegans.

ABSTRACT: Non-coding small RNAs of the micro-RNA class (miRNA) are conserved regulators of gene function with a broad impact on biological processes. We screened miRNA levels for age-related changes in individual worms and investigated their influence on the lifespan of the nematode C. elegans. We measured the abundance of 69 miRNAs expressed in individual animals at different ages with over thirty five thousand discrete quantitative nano-fluidic polymerase chain reactions. We found that miRNA abundance was highly variable between individual worms raised under identical conditions and that expression variability generally increased with age. To identify expression differences associated with either reproductive or somatic tissues, we analyzed wild type and mutants that lacked germlines. miRNAs from the mir-35-41 cluster increased in abundance with age in wild type animals, but were nearly absent from mutants lacking a germline, suggesting their age-related increase originates from the germline. Most miRNAs with age-dependent levels did not have a major effect on lifespan, as corresponding deletion mutants exhibited wild-type lifespans. The major exception to this was mir-71, which increased in abundance with age and was required for normal longevity. Our genetic characterization indicates that mir-71 acts at least partly in parallel to insulin/IGF like signals to influence lifespan.

SUBMITTER: Lucanic M

PROVIDER: S-EPMC3824409 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Age-related micro-RNA abundance in individual C. elegans.

Lucanic Mark M Graham Jill J Scott Gary G Bhaumik Dipa D Benz Christopher C CC Hubbard Alan A Lithgow Gordon J GJ Melov Simon S

Aging 20130601 6

Non-coding small RNAs of the micro-RNA class (miRNA) are conserved regulators of gene function with a broad impact on biological processes. We screened miRNA levels for age-related changes in individual worms and investigated their influence on the lifespan of the nematode C. elegans. We measured the abundance of 69 miRNAs expressed in individual animals at different ages with over thirty five thousand discrete quantitative nano-fluidic polymerase chain reactions. We found that miRNA abundance w ...[more]

PMID: 23793570

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Project description:Results: MiRNA expression profiling of 1281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant with data from other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. This finding was supported by exploratory analysis of predicted time effects from the mixed effects models. Furthermore, no significant effect of ASA could be found. Concerning the functional implication of the 20 most abundantly expressed miRNAs, we found 6 functional themes: nuclear import, cell cycle, transmembrane receptor protein serine/threonine kinase signaling pathway, regulation of kinase activity, pathways in cancer, and leukocyte differentiation. Conclusion: Our study shows that the platelet miRNA profile is remarkably stable in healthy subjects and is not affected by single-dose ASA treatment. For this reason, single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward additional extra-platelet effects of platelet miRNAs. We assessed the platelet miRNA profile blood in 5 volunteers at five time points over a time course of 10 days; 24 h prior to the last blood sampling, all subjects took 500 mg acetylsalicylic acid (ASA) once. Platelet miRNA was isolated from platelet-rich plasma which was leucocyte-depleted by negative bead separation. Then miRNA array analysis was performed on the isolated platelet miRNA. Temporal patterns and the effect of ASA were explored by a linear mixed effects model for each miRNA. For the 20 most abundantly expressed platelet miRNAs, a target gene search was performed by using miRWalk for validated and predicted targets. To visualize which molecular functions arerelated to those miRNAs, an annotation network was created by ClueGO, a Cytoscape plug-in.

Project description:BackgroundAge-related muscle decline (sarcopenia) associates with numerous health risk factors and poor quality of life. Drugs that counter sarcopenia without harmful side effects are lacking, and repurposing existing pharmaceuticals could expedite realistic clinical options. Recent studies suggest bisphosphonates promote muscle health; however, the efficacy of bisphosphonates as an anti-sarcopenic therapy is currently unclear.MethodsUsing Caenorhabditis elegans as a sarcopenia model, we treated animals with 100 nM, 1, 10, 100 and 500 μM zoledronic acid (ZA) and assessed lifespan and healthspan (movement rates) using a microfluidic chip device. The effects of ZA on sarcopenia were examined using GFP-tagged myofibres or mitochondria at days 0, 4 and 6 post-adulthood. Mechanisms of ZA-mediated healthspan extension were determined using combined ZA and targeted RNAi gene knockdown across the life-course.ResultsWe found 100 nM and 1 μM ZA increased lifespan (P < 0.001) and healthspan [954 ± 53 (100 nM) and 963 ± 48 (1 μM) vs. 834 ± 59% (untreated) population activity AUC, P < 0.05]. 10 μM ZA shortened lifespan (P < 0.0001) but not healthspan (758.9 ± 37 vs. 834 ± 59, P > 0.05), whereas 100 and 500 μM ZA were larval lethal. ZA (1 μM) significantly improved myofibrillar structure on days 4 and 6 post-adulthood (83 and 71% well-organized myofibres, respectively, vs. 56 and 34% controls, P < 0.0001) and increased well-networked mitochondria at day 6 (47 vs. 16% in controls, P < 0.01). Genes required for ZA-mediated healthspan extension included fdps-1/FDPS-1 (278 ± 9 vs. 894 ± 17% population activity AUC in knockdown + 1 μM ZA vs. untreated controls, respectively, P < 0.0001), daf-16/FOXO (680 ± 16 vs. 894 ± 17%, P < 0.01) and agxt-2/BAIBA (531 ± 23 vs. 552 ± 8%, P > 0.05). Life/healthspan was extended through knockdown of igdb-1/FNDC5 (635 ± 10 vs. 523 ± 10% population activity AUC in gene knockdown vs. untreated controls, P < 0.01) and sir-2.3/SIRT-4 (586 ± 10 vs. 523 ± 10%, P < 0.05), with no synergistic improvements in ZA co-treatment vs. knockdown alone [651 ± 12 vs. 635 ± 10% (igdb-1/FNDC5) and 583 ± 9 vs. 586 ± 10% (sir-2.3/SIRT-4), both P > 0.05]. Conversely, let-756/FGF21 and sir-2.2/SIRT-4 were dispensable for ZA-induced healthspan [630 ± 6 vs. 523 ± 10% population activity AUC in knockdown + 1 μM ZA vs. untreated controls, P < 0.01 (let-756/FGF21) and 568 ± 9 vs. 523 ± 10%, P < 0.05 (sir-2.2/SIRT-4)].ConclusionsDespite lacking an endoskeleton, ZA delays Caenorhabditis elegans sarcopenia, which translates to improved neuromuscular function across the life course. Bisphosphonates might, therefore, be an immediately exploitable anti-sarcopenia therapy.

Dataset Information

Age-related micro-RNA abundance in individual C. elegans.

Publications

Age-related micro-RNA abundance in individual C. elegans.

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