title: Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects.
abstract: Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories. Reproducibility between test sites is high, whereas individual trial reproducibility is relatively low. Of ten pro-longevity chemicals tested, six significantly extend lifespan in at least one strain. Three reported dietary restriction mimetics are mainly effective across C. elegans strains, indicating species and strain-specific responses. In contrast, the amyloid dye ThioflavinT is both potent and robust across the strains. Our results highlight promising pharmacological leads and demonstrate the importance of assessing lifespans of discrete cohorts across repeat studies to capture biological variation in the search for reproducible ageing interventions.
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lucanic
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: W Todd
authors.initials: WT
authors.lastname: Plummer
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Esteban
authors.initials: E
authors.lastname: Chen
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Jailynn
authors.initials: J
authors.lastname: Harke
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Foulger
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Onken
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Coleman-Hulbert
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Dumas
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Guo
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Johnson
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Dipa
authors.initials: D
authors.lastname: Bhaumik
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Xue
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Anna B
authors.initials: AB
authors.lastname: Crist
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Presley
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Girish
authors.initials: G
authors.lastname: Harinath
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sedore
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Chamoli
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Shaunak
authors.initials: S
authors.lastname: Kamat
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Chen
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Angeli
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Chang
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Willis
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Edgar
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Royal
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Chao
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Shobhna
authors.initials: S
authors.lastname: Patel
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Theo
authors.initials: T
authors.lastname: Garrett
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ibanez-Ventoso
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: June
authors.initials: J
authors.lastname: Hope
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Kish
authors.affiliation: Division of Aging Biology, National Institute on Aging, 7201 Wisconsin Avenue, Bethesda, Maryland 20892-9205, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Guo
authors.affiliation: The Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lithgow
authors.affiliation: Nelson Biological Laboratories, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Driscoll
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, Oregon 97403, USA.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Phillips
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D002107:Caenorhabditis / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005298:Fertility / Q000187:drug effects / Q000235:genetics; D000068617:Genetic Background; D008136:Longevity / Q000187:drug effects* / Q000235:genetics; D009930:Organic Chemicals / Q000494:pharmacology*; D015203:Reproducibility of Results; D013045:Species Specificity; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; D009930:Organic Chemicals; D013844:Thiazoles; C009462:thioflavin T