Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans.

Devon Chandler-Brown,Shirley Park,Anna Le,Billie R Ocampo,George L Sutphin,Shiwen Chen,Matt Kaeberlein,Lara S Shamieh,Erica D Smith,Haeri Choi

doi:10.3389/fgene.2015.00316

Devon Chandler-Brown, Shirley Park + Show 8 more

Open Access

https://doi.org/10.3389/fgene.2015.00316

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Abstract

The response to osmotic stress is a highly conserved process for adapting to changing environmental conditions. Prior studies have shown that hyperosmolarity by addition of sorbitol to the growth medium is sufficient to increase both chronological and replicative lifespan in the budding yeast, Saccharomyces cerevisiae. Here we report a similar phenomenon in the nematode Caenorhabditis elegans. Addition of sorbitol to the nematode growth medium induces an adaptive osmotic response and increases C. elegans lifespan by about 35%. Lifespan extension from 5% sorbitol behaves similarly to dietary restriction in a variety of genetic backgrounds, increasing lifespan additively with mutation of daf-2(e1370) and independently of daf-16(mu86), sir-2.1(ok434), aak-2(ok524), and hif-1(ia04). Dietary restriction by bacterial deprivation or mutation of eat-2(ad1113) fails to further extend lifespan in the presence of 5% sorbitol. Two mutants with constitutive activation of the osmotic response, osm-5(p813) and osm-7(n1515), were found to be long-lived, and lifespan extension from sorbitol required the glycerol biosynthetic enzymes GPDH-1 and GPDH-2. Taken together, these observations demonstrate that exposure to sorbitol at levels sufficient to induce an adaptive osmotic response extends lifespan in worms and define the osmotic stress response pathway as a longevity pathway conserved between yeast and nematodes.

Highlights

Studies in model organisms have demonstrated that aging can be influenced by a combination of genetic and environmental factors (Fontana et al, 2010; Kaeberlein, 2010; Kenyon, 2010)
Longevity analysis in C. elegans is typically performed by maintaining animals on the surface of a nutrient-agar medium with a lawn of E. coli OP50 as the food source
A simple and robust method of dietary restriction (DR) for C. elegans has been described, in which animals are cultured in the standard conditions until early adulthood, at which time the OP50 food source is removed for the remainder of life (Kaeberlein et al, 2006; Lee et al, 2006; Smith et al, 2008; Sutphin and Kaeberlein, 2008)

Summary

Introduction

Studies in model organisms have demonstrated that aging can be influenced by a combination of genetic and environmental factors (Fontana et al, 2010; Kaeberlein, 2010; Kenyon, 2010). Genomescale screens in both yeast and nematodes, for example, have identified several hundred genes that modulate lifespan, and multiple single-gene mutations have been shown to increase lifespan in rodents (Smith et al, 2007a; Yanos et al, 2012). DR has been shown to enhance longevity and healthspan in a variety of different organisms including yeast, nematodes, flies, mice, dogs, and rhesus monkeys (Kennedy et al, 2007; Omodei and Fontana, 2011; Colman et al, 2014). One mechanism by which DR is thought to modulate aging is by reducing signaling through the mechanistic target of rapamycin (mTOR) kinase (Kapahi et al, 2010; Johnson et al, 2013)

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