SPATIOTEMPORAL REGULATION OF AUTOPHAGY DURING CAENORHABDITIS ELEGANS AGING

Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

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Autophagy has been linked to longevity in turbo air m3f24-1-n many species, but the underlying mechanisms are unclear.Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood.Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals.In contrast, daf-2 and glp-1 mutants displayed unique age- and tissue-specific changes in autophagic activity, indicating that the two longevity paradigms have distinct effects on autophagy during aging.Although autophagy appeared active in the intestine of both nightstick twm-850xl long-lived mutants, inhibition of intestinal autophagy significantly abrogated lifespan extension only in glp-1 mutants.

Collectively, our data suggest that autophagic activity normally decreases with age in C.elegans, whereas daf-2 and glp-1 long-lived mutants regulate autophagy in distinct spatiotemporal-specific manners to extend lifespan.

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