Long-Lived
            <i>C. elegans daf-2</i>
            Mutants Are Resistant to Bacterial Pathogens

Garsin, Danielle A.; Villanueva, Jacinto M.; Begun, Jakob; Kim, Dennis H.; Sifri, Costi D.; Calderwood, Stephen B.; Ruvkun, Gary; Ausubel, Frederick M.

doi:10.1126/science.1080147

Cited by 563 publications

(578 citation statements)

References 7 publications

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“…Also, in vivo studies indicate that the FOXO-dependent regulation of AMPs is evolutionarily conserved (see also (Becker et al, 2010;Garsin et al, 2003;Troemel et al, 2006)). Becker et al (2010) found that AMP expression was inhibited in FOXO null mutants but enhanced when FOXO was overexpressed.…”

Section: Nutrition and The Consequences Of Immune Trade-offsmentioning

confidence: 99%

Integrating nutrition and immunology: A new frontier

Ponton

Wilson

Holmes

et al. 2013

Journal of Insect Physiology

129

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Section: Nutrition and The Consequences Of Immune Trade-offsmentioning

confidence: 99%

Integrating nutrition and immunology: A new frontier

Ponton

Wilson

Holmes

et al. 2013

Journal of Insect Physiology

129

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“…In particular, mutations in the daf-2 insulin-like receptor extend lifespan up to one fold [20,21]. daf-2 mutant worms are also more resistant to a variety of stress conditions and less susceptible to tumorigenesis than are wild-type worms [8,26,28,31]. To ascertain whether and how the daf-2 gene affects the rate of motor activity decay, we quantified spontaneous locomotion behavior of daf-2 (e1370) and daf-2(e1368) worms throughout their lifesapn.…”

Section: Mutations That Extend Lifespan Reduce the Rate Of Motor Actimentioning

confidence: 99%

Identification by machine vision of the rate of motor activity decline as a lifespan predictor in C. elegans

Hsu

Feng

Hsieh

et al. 2009

Neurobiology of Aging

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One challenge in aging research concerns identifying physiological parameters or biomarkers that can reflect the physical health of an animal and predict its lifespan. In C. elegans, a model organism widely used in aging research, motor deficits develop in old worms. Here we employed machine vision to quantify worm locomotion behavior throughout lifespan. We confirm that aging worms undergo a progressive decline in motor activity, beginning in early life. Importantly, the rate of motor activity decline rather than the absolute motor activity in the early-to-mid life of individual worms in an isogenic population inversely correlates with their lifespan, and thus may serve as a lifespan predictor. Long-lived mutant strains with deficits in insulin/IGF-1 signaling or food intake display a reduction in the rate of motor activity decline, suggesting that this parameter might also be used for across-strain comparison of healthspan. Our work identifies an endogenous physiological parameter for lifespan prediction and healthspan comparison.

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“…Because a conserved insulin-like signaling pathway controls both aging and pathogen resistance in Caenorhabditis elegans (2,3), the identification of cellular innate immune functions regulated by this pathway may help elucidate the basis of age-related declines in immunity. One candidate target is autophagy, a lysosomal degradation pathway that decreases with age, is implicated in the degradation of intracellular bacteria, and is required for the lifespan extension of nematodes with mutation in the daf-2 insulin-like signaling pathway (4)(5)(6)(7).…”

mentioning

confidence: 99%

Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance

Jia¹,

Thomas²,

Akbar³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

201

195

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A conserved insulin-like pathway modulates both aging and pathogen resistance in Caenorhabditis elegans. However, the specific innate effector functions that mediate this pathogen resistance are largely unknown. Autophagy, a lysosomal degradation pathway, plays a role in controlling intracellular bacterial pathogen infections in cultured cells, but less is known about its role at the organismal level. We examined the effects of autophagy gene inactivation on Salmonella enterica Serovar Typhimurium (Salmonella typhimurium) infection in 2 model organisms, Caenorhabditis elegans and Dictyostelium discoideum. In both organisms, genetic inactivation of the autophagy pathway increases bacterial intracellular replication, decreases animal lifespan, and results in apoptotic-independent death. In C. elegans, genetic knockdown of autophagy genes abrogates pathogen resistance conferred by a loss-of-function mutation, daf-2(e1370), in the insulin-like tyrosine kinase receptor or by overexpression of the DAF-16 FOXO transcription factor. Thus, autophagy genes play an essential role in host defense in vivo against an intracellular bacterial pathogen and mediate pathogen resistance in long-lived mutant nematodes.

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Long-Lived C. elegans daf-2 Mutants Are Resistant to Bacterial Pathogens

Cited by 563 publications

References 7 publications

Integrating nutrition and immunology: A new frontier

Integrating nutrition and immunology: A new frontier

Identification by machine vision of the rate of motor activity decline as a lifespan predictor in C. elegans

Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance

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