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[CRON4healthyfuture]

A fascinating new paper indicates that 24 hours of "starvation" gets DAF-16 into the nucleus, but longer term starvation sends it back out.

What is the importance of this? Well, the researchers painstakingly showed that ageing itself produces a gradual efflux of DAF-16 from the nucleus. They found that whenever you could get that DAF-16 to say inside the nucleus, you produce a hardier worm. Whenever it pops back out, that worm becomes a "loser".

Interestingly, the PI3K insulinemic axis was shown to keep DAF-16 outside of the nucleus. So trying to eat in a way that minimizes signaling through this axis would be benefical it would seem.

In regards to eating patterns, this would at the very least suggest that there may be some benefit to the "on/off" pattern of "feeding/fasting", but of course, more research is needed.

And the full-text is free to everyone, and their pet dog (worm?) too.........

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Click Here!!

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"Reduction-of-function mutations in AGE-1, the C. elegans Class IA phosphoinositide 3-kinase (PI3K), increase lifespan and stress resistance in a daf-16 dependent manner. Class IA PI3Ks downregulate FOXOs by inducing their translocation to the cytoplasm. However, the circumstances under which AGE-1 is normally activated are unclear. To address this question we used C. elegans first stage larvae (L1s), which when starved enter a developmentally-arrested diapause stage until food is encountered. RESULTS: We find that in L1s both starvation and daf-16 are necessary to confer resistance to oxidative stress in the form of hydrogen peroxide. Accordingly, DAF-16 is localised to cell nuclei after short-term starvation. However, after long-term starvation, DAF-16 unexpectedly translocates to the cytoplasm. This translocation requires functional age-1. H2O2 treatment can replicate the translocation and induce generation of the AGE-1 product PIP3. Because feeding reduces to zero in ageing adult C. elegans, these animals may also undergo long-term starvation. Consistent with our observation in L1s, DAF-16 also translocates to the cytoplasm in old adult worms in an age-1-dependent manner. CONCLUSIONS: DAF-16 is activated in the starved L1 diapause. The translocation of DAF-16 to the cytoplasm after long-term starvation may be a feedback mechanism that prevents excessive expenditure on stress resistance. H2O2 is a candidate second messenger in this feedback mechanism. The lack of this response in age-1(hx546) mutants suggests a novel mechanism by which this mutation increases longevity."

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