Impact of worm genetic background on lifespan extension result (CITP)

#1

TLDR: From 6 drugs that extended lifespan in C Elegans, only 1 extended lifespan in other strains of worms, Rapamycin wasn’t tested here

https://www.nature.com/articles/ncomms14256

  • CITP tested 12 drugs that allegedly extended lifespan in C Elegans

  • 6 worked in C Elegans, from this only 1 tested drug worked on all 3 strains of worms (C Elegans, C Briggsae, C Tropicalis)

  • What worked on all 3 strains of worms? Thioflavin T

  • What worked only on C Elegans but not other? NP1, AKG, Resveratol, Propyl Gallate, Alpha lipoic acid

  • Rapamycin, Rapalogs, Acarbose or 17 alfa estradiol weren’t tested here

  • Effects are usually the biggest in N2 type of C Elegans - because almost all drugs that extended lifespan were tested on N2 type of C Elegans (which means that there is a problem in longevity research - because everything focus on only this type of animal)

  • C Elegans, C Tropicalis and C Briggsae have about 30 - 100 mln years of evolutionary genetic difference, almost the same difference as humans and mice

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Suggestions for ITP drugs to test
#2

Thanks. This is important. We are searching for our lost key under the streetlight because the light is better there.

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#3

Yes. This wasn’t an unexpected result, IMO. Caenorhabditis have quite a bit of life history plasticity that makes results hard to interpret for them.

Digging deeper, thioflavin T, while too toxic for mammals, has an analog called “HBX”, which is similarly effective in (at least one strain of!) worms, and has some evidence in mouse disease models. It got a null result in the (mouse) ITP. Similarly, it seems from published abstracts (without data) that metformin prolongs lifespan robustly in Caenorhabditis. It too has not been successful as a monotherapy in mice.

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#4

Only when started early in life, when it is started when C Elegans is adult, then Metformin extends lifespan only by 5%, when started late in life, it shortens lifespan of C Elegans