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Citation
Schmeisser S, Priebe S, Groth M, Monajembashi S, Hemmerich P, Guthke R, Platzer M, Ristow M.
Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension.
Mol Metab
, 2013.
PubMed ID
24199155
Short Description
Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension.
GEO Record: N.A. Platform: N.A.
Download gene-centric, log2 transformed data:
WBPaper00044426.ce.rs.csv
# of Conditions
22
Full Description
Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. DR is widely believed to promote longevity by causing an energy deficit leading to increased mitochondrial respiration. We here show that inhibitors of mitochondrial complex I promote physical activity, stress resistance as well as lifespan of Caenorhabditis elegans despite normal food uptake, i.e. in the absence of DR. However, complex I inhibition does not further extend lifespan in dietarily restricted nematodes, indicating that impaired complex I activity mimics DR. Promotion of longevity due to complex I inhibition occurs independently of known energy sensors, including DAF-16/FoxO, as well as AAK-2/AMPK and SIR-2.1/sirtuins, or both. Consistent with the concept of mitohormesis, complex I inhibition transiently increases mitochondrial formation of reactive oxygen species (ROS) that activate PMK-1/p38 MAP kinase and SKN-1/NRF-2. Interference with this retrograde redox signal as well as ablation of two redox-sensitive neurons in the head of the worm similarly prevents extension of lifespan. These findings unexpectedly indicate that DR extends organismal lifespan through transient neuronal ROS signaling rather than sensing of energy depletion, providing unexpected pharmacological options to promote exercise capacity and healthspan despite unaltered eating habits.
Experimental Details:
RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265354
RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265355
RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265356
RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265357
RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265358
RNASeq.elegans.WBStrain00000001.WBls:0000064.Hermaphrodite.WBbt:0007833.SRP021083.SRX265359
RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265360
RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265361
RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265362
RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265363
RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265364
RNASeq.elegans.WBStrain00000001.WBls:0000068.Hermaphrodite.WBbt:0007833.SRP021083.SRX265365
RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265366
RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265367
RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265368
RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265369
RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265370
RNASeq.elegans.WBStrain00000001.WBls:0000674.Hermaphrodite.WBbt:0007833.SRP021083.SRX265371
RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265372
RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265373
RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265374
RNASeq.elegans.WBStrain00000001.WBls:0000676.Hermaphrodite.WBbt:0007833.SRP021083.SRX265375
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Tags
Method: RNAseq, Species: Caenorhabditis elegans, Topic: response to chemical