Publications


Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis

      Xie, Y. et al.
     bioRxiv  2024 Jun 30:2024.06.30.600712

     Pub30  DOI30
  • Fig. 1Cell type-specific proteomics characterize visual experience-dependent nascent protein dynamics
  • Fig. 2Emerin is an activity-regulated protein
  • Fig. 3Acute activity-induced Emerin expression is driven directly by translation
  • Fig. 4Emerin bidirectionally regulates protein synthesis including translation factors and synaptic proteins
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Quantifying Food Intake in Caenorhabditis elegans by Measuring Bacterial Clearance

     Clark, C. et al.
     Jove  2024 Feb 23:(204)

     Pub29  DOI29
  • Fig. 1Schematic of the bacterial clearance assay
  • Fig. 2Design and analysis
  • Fig. 3Representative Results
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Proteostasis is differentially modulated by inhibition of translation initiation or elongation

     Clay, KJ. et al.
     ELife  2023 Oct 5:12:e76465

     Pub28  DOI28
  • Fig. 1Identifying mechanistic inhibitors of protein synthesis in C. elegans
  • Fig. 2Initiation but not elongation inhibitors depend on HSF-1 to protect C. elegans from thermal stress
  • Fig. 3Elongation inhibitors reduce the number of heat shock-induced protein aggregates
  • Fig. 4Elongation inhibitors protect C. elegans from proteasomal stress independent of hsf-1
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Targeting Clic1 for the treatment of obesity: A novel therapeutic strategy to reduce food intake and body weight

     Zapata, RC. et al.
     Mol Metab  2023 Oct:76:101794

     Pub26  DOI26
  • Fig. 1Hypothalamic Expression of Clic1
  • Fig. 2Whole body knockout of Clic1 is associated with lower food intake and body weight
  • Fig. 3IAA94 mediated reduction in food intake is mediated via Clic1
  • Fig. 4Clic1 inhibition has a dose dependent effect on reducing body weight and has an additional effect on weight loss when given in combination with GLP-1 agonist, Liraglutide
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Adipocytes control food intake and weight regain via Vacuolar-type H+ ATPase

     Zapata, RC. et al.
     Nat Commun  2022 Aug 30;13(1):5092

     Pub26  DOI26
  • Fig. 1Identification of metabolic memory genes in adipose tissue in formerly obese mice
  • Fig. 2V-ATPase expression in obesity
  • Fig. 3Adipocyte-specific Atp6v0a1 depletion in vitro and in vivo
  • Fig. 4Adipocyte-specific Atp6v0a1 KO mice fed HFD gain less weight due to reduced food intake
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Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects

     Strong, R. et al.
     Aging Cell  2020 Nov;19(11):e13269

     Pub25  DOI25
  • Fig. 1Kaplan–Meier survival plots for female and male mice exposed to different Rapa treatment schedules
  • Fig. 2Weight at 6–24 months of age for Control and Rapa‐treated mice, pooled across sites
  • Fig. 3Kaplan–Meier survival plots for female and male mice treated with 17‐DMAG, Min, bGPA, or MitoQ
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A chemical biology approach to identifying molecular pathways associated with aging

     Currais, A. et al.
     Geroscience  2021 Feb;43(1):353-365

     Pub24  DOI24
  • Fig. 1Experimental diagram
  • Fig. 2Aging of the hippocampal transcriptome in SAMP8 mice is significantly prevented by CAD031
  • Fig. 3CAD031 maintains several parameters of mitochondrial metabolism that are altered with aging in SAMP8 mice
  • Fig. 4Effects of CAD031 on brain and plasma metabolites. a Pathway enrichment analysis with cortex metabolites found altered in 13 months vs 13 months+CAD031
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The aging transcriptome: read between the lines

     Perez-Gomez, A. et al.
     Current Opinion in Neurobiology  2020 Aug;63:170-175

     Pub23  DOI23
  • Fig. 1Random and non-random forms of transcriptional degeneration
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Elevating acetyl-CoA levels reduces aspects of brain aging

     Currais, A. et al.
     Elife  2019 Nov 19;8:e47866

     Pub22  DOI22
  • Fig. 1Aging of the hippocampal transcriptome in SAMP8 mice is significantly prevented by CMS121 and J147
  • Fig. 2CMS121 and J147 preserve cognitive parameters in SAMP8 mice when administered at advanced stages of the phenotype
  • Fig. 3CMS121 and J147 specifically maintain the expression of genes associated with the mitochondria that are altered with aging in SAMP8 mice
  • Fig. 4Global metabolic analysis of brain cortex and blood plasma
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Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan

     Chen, A.L. et al.
     Nature Chem.  2019 May;15(5):453-462.

     Pub22  DOI22
  • Fig. 1A chemical proteomic map of serine hydrolase (SH) activities and their chemical inhibition in C. elegans
  • Fig. 2Phenotypic screening identifies SH-directed inhibitors that extend lifespan in C. elegans
  • Fig. 3Identification of FAAH-4 as a principal target of JZL184 in C. elegans
  • Fig. 4FAAH-4 is inhibited by JZL184
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Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart

     Ahuga, G et al.
     EMBO Rep.  2019 Apr 20;(4):e47407

     Pub22  DOI22
  • Fig. 1Killifish hearts show molecular, physiological and metabolic signatures of cardiac ageing
  • Fig. 2Elevated sphinganine levels induce DNA damage without causing apoptosis in cardiomyocytes
  • Fig. 3Elevated sphinganine levels induce genomic instability and ageing signatures in human cardiomyocytes
  • Fig. 4DHS ‐induced genomic instability is a consequence of HDAC inhibition in human cardiomyocytes
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A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia

     Perez-Gomez, A et al.
     Nat Commun  2018 Dec 10;9(1):5272

     Pub21  DOI21
  • Fig. 1AP administration results in hyperphagic response in C. elegans
  • Fig. 2C. elegans based screen of FDA-approved drugs for potential adjuvant to block AP-induced hyperphagia
  • Fig. 3Co-administration of minocycline in mice prevents olanzapine-induced hyperphagia and weight gain
  • Fig. 4RNA sequencing identifies gene expression profile associated with AP-hyperphagia
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Translation attenuation by minocycline enhances longevity and proteostasis in old post-stress-responsive organisms

     Solis, GM. et al.
     Elife  2018 Nov 27;7

     Pub20  DOI20
  • Fig. 1Stress signaling pathway activity declines with age
  • Fig. 2Minocycline suppresses stress signaling pathway activity
  • Fig. 3Minocycline attenuates translation in C. elegans
  • Fig. 4Minocycline attenuates translation and reduces ribosomal load of highly translated mRNAs
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Geroneuroprotectors: Effective Geroprotectors for the Brain

     Shubert, D. et al.
     Trends Pharmacol Sci.  2018 Dec;39(12):1004-1007

     Pub19  DOI19
  • Fig. 1Geroneuroprotectors (GNPs) Share Molecular Pathways with Caloric Restriction and Geroprotectors
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The mitochondrial ATP synthase is a shared drug target for aging and dementia

     Goldberg J. et al.
     Aging Cell  2018 Apr;17(2)

     Pub18  DOI18
  • Fig. 1Target identification by DARTS and affinity precipitation pull‐downs
  • Fig. 2J147 targets mitochondrial bioenergetics
  • Fig. 3Knockdown of ATP5A phenocopies the neuroprotective effects of J147
  • Fig. 4J147 and ATP5A modulate AMPK/mTOR signaling
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Computation Analysis of Lifespan Experiment Reproducibility

     Petrascheck M and Miller DL
     Front Genet.  2017 Jun 30;8:92

     Pub17  DOI17
  • Fig. 1Gompertz-based Parametric Model for C. elegans lifespan
  • Fig. 2Frequent scoring of lifespan strongly affects accuracy of lifespan measurement but only modestly affects power of detection
  • Fig. 3Population size has important effect on power of detection
  • Fig. 4Lifespan extensions caused by changing γ values has little effect on POD
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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

     Pub1  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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