Caenorhabditis Intervention Testing Program: the farnesoid X receptor agonist obeticholic acid does not robustly extend lifespan in nematodes

Morshead, Mackenzie; Sedore, Christine A; Jones, Eleanor G.; Hall, David G.; Plummer, W. Todd; Garrett, Theo; Lucanic, Mark; Guo, Max; Driscoll, Monica; Phillips, Patrick C.; Lithgow, Gordon J.

doi:10.17912/micropub.biology.000257

Cited by 6 publications

(2 citation statements)

References 8 publications

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“…1 Some of these challenges have been met by long-term culturing and imaging 2,3 that have been used for large-scale lifespan analyses. [4][5][6] For example, a recent highthroughput analysis of lifespan and motility traits 7 reemphasized that induced maximum velocity best reflects health of individuals with age, as we previously reported. 8 However, such large-scale approaches usually require the elimination of progeny, limiting the analysis to lifespan and healthspan metrics that ignore reproductive traits and reproductive effects on lifespan.…”

Section: Introductionmentioning

confidence: 83%

CeLab, a microfluidic platform for the study of life history traits, reveals metformin and SGK-1 regulation of longevity and reproductive span

2023

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Section: Introductionmentioning

confidence: 83%

CeLab, a microfluidic platform for the study of life history traits, reveals metformin and SGK-1 regulation of longevity and reproductive span

2023

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“…C. elegans assays often require a large sample size and frequent physical manipulations, rendering them highly labor-intensive 1 . Some of these challenges have been met by long-term culturing and imaging 2,3 that have been used for large-scale lifespan analyses 4–6 . For example, a recent high-throughput analysis of lifespan and motility traits 7 re-emphasized that induced Maximum Velocity best reflects health of individuals with age, as we previously reported 8 .…”

Section: Introductionmentioning

confidence: 99%

CeLab, a Microfluidic Platform for the Study of Life History Traits, reveals Metformin and SGK-1 regulation of Longevity and Reproductive Span

Sohrabi

Cota

Murphy

2023

Preprint

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The potential to carry out high-throughput assays in a whole organism in a small space is one of the benefits of C. elegans, but worm assays often require a large sample size with frequent physical manipulations, rendering them highly labor-intensive. Microfluidic assays have been designed with specific questions in mind, such as analysis of behavior, embryonic development, lifespan, and motility. While these devices have many advantages, current technologies to automate worm experiments have several limitations that prevent widespread adoption, and most do not allow analyses of reproduction-linked traits. We developed a miniature C. elegans lab-on-a-chip device, CeLab, a reusable, multi-layer device with 200 separate incubation arenas that allows progeny removal, to automate a variety of worm assays on both individual and population levels. CeLab enables high-throughput simultaneous analysis of lifespan, reproductive span, and progeny production, refuting assumptions about the Disposable Soma hypothesis. Because CeLab chambers require small volumes, the chip is ideal for drug screens; we found that drugs previously shown to increase lifespan also increase reproductive span, and we discovered that low-dose metformin increases both. CeLab reduces the limitations of escaping and matricide that typically limit plate assays, revealing that feeding with heat-killed bacteria greatly extends lifespan and reproductive span of mated animals. CeLab allows tracking of life history traits of individuals, which revealed that the nutrient-sensing mTOR pathway mutant, sgk-1, reproduces nearly until its death. These findings would not have been possible to make in standard plate assays, in low-throughput assays, or in normal population assays.

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Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes

Banse,

Sedore,

Johnson

et al. 2023

GeroScience

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The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies—for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.

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Caenorhabditis Intervention Testing Program: the farnesoid X receptor agonist obeticholic acid does not robustly extend lifespan in nematodes

Cited by 6 publications

References 8 publications

CeLab, a microfluidic platform for the study of life history traits, reveals metformin and SGK-1 regulation of longevity and reproductive span

CeLab, a microfluidic platform for the study of life history traits, reveals metformin and SGK-1 regulation of longevity and reproductive span

CeLab, a Microfluidic Platform for the Study of Life History Traits, reveals Metformin and SGK-1 regulation of Longevity and Reproductive Span

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes

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