The DrugAge database of aging-related drugs

     Barardo D, et al.
     Aging Cell  2017 Jun;16(3):594-597

     Pub16  DOI16
  • Fig. 1Several snapshots of DrugAge's Web interface
  • Fig. 2DrugAge analyses and functional enrichment
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C. elegans as Model for Drug Discovery

     Carretero M, Solis GM, Petrascheck M
     Curr Top Med Chem.  2017 Jan 31; 17(32)

     Pub15  DOI15

Mood, stress and longevity: convergence on ANK3

     Rangaraju S, Levey DF, Nho K, Jain N, Andrews KD, Le-Niculescu H, Salomon DR, Saykin AJ, Petrascheck M, Niculescu AB
     Mol Psychiatry  2016 Aug; 21(8):1037-49

     Pub14  DOI14
  • Fig. 1Flowchart of studies
  • Fig. 2Human GWAS. Identifying SNPs associated with depressive symptoms in an aging cohort using an extreme trait design
  • Fig. 3Convergent functional genomics
  • Fig. 4The antidepressant mianserin requires ANK3/unc-44 to protect C. elegans from oxidative stress and to extend lifespan
  • Fig. 5ANK3 and survival
  • Fig. 6ANK3 as a gene expression biomarker for biological age
  • Fig. 7Proposed mechanistic cascade
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Metabolic drift in the aging brain

     Ivanisevic J, et al.
     Aging  2016 May; 8(5):1000-20

     Pub13  DOI13
  • Fig. 1Experimental design of comprehensive regional and temporal profiling of murine brain proteome and metabolome
  • Fig. 2Hippocampal proteomic changes from 12 to 24 months
  • Fig. 3Metabolic changes and associated affected pathways in aged mouse brain using global metabolomic approach
  • Fig. 4Metabolome drift in the aged murine brain
  • Fig. 5Metabolite level changes in core metabolism of aged mouse brain
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Proton Pump Inhibitors Accelerate Endothelial Senescence

     Yepuri G, Sukhovershin R, Nazari-Shafti TZ, Petrascheck M, Ghebre YT, Cooke JP
     Circ Res. 2016 Jun 10;118(12)

     Pub12  DOI12
  • Fig. 1Esomeprazole impairs proteostasis
  • Fig. 2Esomeprazole impairs endothelial function
  • Fig. 3Proton pump inhibitors (PPIs) accelerate endothelial senescence
  • Fig. 4Proton pump inhibitors reduce telomere length and expression of shelterin complex subunits
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C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension

     McQuary P, et al.
     Cell Reports  2016 Mar 08; 14(9):2059-677

     Pub11  DOI11
  • Fig. 1Graphical abstract
  • Fig. 2argk-1 Is Selectively Required for the Long Lifespan of rsks-1/S6K Mutants
  • Fig. 3argk-1 Is Required for Increased AMPK Activity in rsks-1/S6K Mutants
  • Fig. 4aak-2/AMPK Contributes to Lifespan Extension by Overexpression of ARGK-1
  • Fig. 5Creatine Kinase Expression Is Increased in the Cerebellums of S6K−/− Mice
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Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality

     Rangaraju S, Solis GM, Thompson R, Gomez-Amaro R, Kurian L, Encalada S, Niculescu III A, Salomon D, Petrascheck M
     eLife  2015 Dec 01; 6:77

     Pub10  DOI10
  • Fig. 1Transcriptional drift-variance increases with age.
  • Fig. 2Transcriptional drift-variance is attenuated by two longevity paradigms.
  • Fig. 3Preserving low drift-variances in redox pathways preserves redox capacity into old age.
  • Fig. 4Preserving redox capacity into old age requires the serotonin receptor SER-5.
  • Fig. 5Mianserin attenuates drift-variance in peripheral tissues via SER-5.
  • Fig. 6Mianserin extends lifespan by specifically slowing age-associated changes in early adulthood.
  • Fig. 7Transcriptional drift-variance increases with age in various species.
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Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non-cell-autonomous stress response

     Rangaraju S, Solis GM, Andersson S, Gomez-Amaro R, Kardakaris R, Broaddus C, Niculescu III A, Petrascheck M
     Aging Cell  2015 Aug 08; 14(6): 971-981

     Pub9  DOI9
  • Fig. 1The atypical antidepressant Mianserin increases synaptic transmission and resistance to oxidative stress.
  • Fig. 2Mianserin activates a protective oxidative stress response.
  • Fig. 3Mianserin-mediated activation of the oxidative stress response is dependent on synaptic transmission and chemosensation.
  • Fig. 4Reactive oxygen species-mediated activation of the oxidative stress response is independent of synaptic transmission.
  • Fig. 5Lifespan extension and protection from oxidative stress by Mianserin require similar genes.
  • Fig. 6Neuronal versus cell-autonomous activation of the oxidative stress response.
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Measuring Food Intake and Nutrient Absorption in Caenorhabditis elegans

     Gomez-Amaro R, Valentine E, Carretero M, LeBoeuf S, Rangaraju S, Broaddus C, Solis GM, Williamson J, Petrascheck M
     Genetics  2015 Jun; 200(2):443-54

     Pub8  DOI8
  • Fig. 1Measurement of bacterial clearance with C. elegans.
  • Fig. 2Body size influences food intakes.
  • Fig. 3Modulation of food intake by serotonergic signaling.
  • Fig. 4Measurement of nutrient absorption in C. elegans using metabolic labeling coupled with quantitative mass spectrometry.
  • Fig. 5Pulse-feeding assay.
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Pharmacological classes that extend lifespan of Caenorhabditis elegans

     Carretero M, Gomez-Amaro R, Petrascheck M
     Front. Genet.  2015 Mar 03; 6:77

     Pub7  DOI7

High-throughput small-molecule screening in Caenorhabditis elegans

     Rangaraju S, Solis GM, Petrascheck M
     Methods Mol. Biol.  2015 Dec 22;1263:139-551

     Pub6  DOI6
  • Table 1Compound Screening Libraries.
  • Fig. 1Examples of C. elegans phenotypes that can be imaged in 96-well plates.
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The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR

     Chin RM, et al.
     Nature  2014 Jun 19;509(7505):397-401

     Pub5  DOI5
  • Fig. 1a-KG extends the adult lifespan of C. elegans.
  • Fig. 2a-KG binds and inhibits ATP synthase.
  • Fig. 3a-KG longevity is mediated through ATP synthase and the dietary restriction/TOR axis.
  • Fig. 4Inhibition of ATP synthase by a-KG causes a conserved decrease in TOR pathway activity.
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A pharmacological network for lifespan extension in Caenorhabditis elegans

     Ye X, Linton JM, Schork NJ, Buck LB, Petrascheck M
     Aging Cell  2014 Apr;13(2):206-15

     Pub4  DOI4
  • Fig. 1Overview of screening strategy and results.
  • Fig. 2Numerous compounds increase Caenorhabditis elegans lifespan.
  • Fig. 3Many compounds protect Caenorhabditis elegans from oxidative stress.
  • Fig. 4Correlation between effects of compounds on lifespan and stress resistance.
  • Fig. 5Pharmacological network for lifespan extension.
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Measuring Caenorhabditis elegans life span in 96 well microtiter plates

     Solis GM, Petrascheck M
     J Vis Exp.  2011 Mar 18;(49). pii: 2496

     Pub3  DOI3
  • The microtiter plate based lifespan assay accurately reproduces changes in lifespan reported in the literature.
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A high-throughput screen for chemicals that increase the lifespan of Caenorhabditis elegans

     Petrascheck M, Ye X, Buck LB
     Ann N Y Acad Sci.  2009 Jul;1170:698-701

     Pub2  DOI2
  • Extension of C. eleganslifespan by mianserin.
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An antidepressant that extends lifespan in adult Caenorhabditis elegans

     Petrascheck M, Ye X, Buck LB
     Nature 2007 Nov 22;450(7169):553-6

     Pub  DOI1
  • Fig. 1Increases in C. elegans lifespan by human serotonin receptor antagonists require serotonin and octopamine signalling.
  • Fig. 2Mianserin and methiothepin are antagonists of SER-3 octopamine and SER-4 serotonin receptors.
  • Fig. 3Lifespan extension by mianserin and dietary restriction are related.
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