Issue 12, 2023

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

Abstract

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
09 jan 2023
Accepted
05 mei 2023
First published
08 mei 2023

Lab Chip, 2023,23, 2738-2757

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

S. Sohrabi, V. Cota and C. T. Murphy, Lab Chip, 2023, 23, 2738 DOI: 10.1039/D3LC00028A

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