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Sunday, 17 December 2017 20:33

Escherichia Extends elegans Existence - BacterioFiles 321

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Published in Bacteriofiles

This episode: Bacteria with various gene knockouts help roundworms live longer and with less disease!

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(9.9 MB, 10.75 minutes)

Show notes: 

bf297elegansNews item

Journal Paper:
Han B, Sivaramakrishnan P, Lin C-CJ, Neve IAA, He J, Tay LWR, Sowa JN, Sizovs A, Du G, Wang J, Herman C, Wang MC. 2017. Microbial Genetic Composition Tunes Host Longevity. Cell 169:1249–1262.e13.

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Episode outline:

  • Background: What more sought than elixir of youth? Or fountain
    • As old as history, epic of Gilgamesh
  • Modern science many advances in extending life expectancy
    • Sanitation, medicine, agriculture/food security
  • More promising findings to come sometime
    • Telomeres, mental health, etc
  • But low-hanging fruit has been picked
  • What’s new: Now, scientists publishing in Cell have created strains of gut bacteria that extend the healthy life of tiny roundworms!
  • Methods: Pretty hard to study in mammals
    • Bigger and more complex and longer lifespans
  • So chose nematode Caenorhabditis elegans
    • Well-understood lifespan and microbiota
    • In lab often contain only E. coli, on which they feed
  • Used set of E. coli strains with each gene knocked out one at a time (except essential genes)
    • Keio collection, resistance marker insertions
    • Grew roundworms on each of these strains to see effects, 3983 mutants
  • To avoid confusion of worms reproducing and making more worms, used mutant strain
    • Grows and reproduces normally, but embryos die at 25C
    • Look at only the desired generation and see how long it survives
  • With 68 of the mutant bacterial strains, nematodes lived longer
    • 23-35 (depending on microbe genetic background) extended by >10%
    • No common function for these genes, various different functional groups
    • 21 also extended life even when encountered as adult worms, not even exposed early
  • But how? Tested worm strains with specific age-related problems
    • In worms prone to tumors, 16 bacterial strains increased survival rate
    • In worms producing human Alzheimer’s-associated protein (amyloid beta)
      • 14 strains increase lifespan, and 12 delay loss of function
    • Overall, 13 protect against both problems
  • Some mechanisms known for longer roundworm life
    • Insulin-like growth factor, caloric restriction
    • Used worm strains with knockouts of genes related to these pathways
      • Many helpful bacteria were then unable to extend lifespan of these worms
      • Confirms relevance of mechanisms
    • Except for caloric restriction, which seemed unrelated to bacterial effects
  • Found 2 mutants that worked independently of all tested mechanisms
    • Both mutants in genes related to production of metabolite colanic acid
    • Polysaccharide secreted by some enterobacteria
    • Both mutants produced more colanic acid than usual
    • Deleting colanic acid production in these mutants removed life extension effect
      • Fully or partially, depending on strain
    • So colanic acid seems part of effect but not whole
    • Seems to help preserve mitochondrial function, works in other species too
  • Also tried colanic acid directly, independent from bacteria
    • Works just as well
    • Also helps fruit flies too
    • Doesn’t work by inhibiting bacterial growth or pathogens; actually sorta helps them
  • Applications and implications: Worth exploring for health effects beyond nematodes
    • Helpful for understanding mechanisms of aging and longevity
    • Possible clue toward probiotics or helpful chemicals
  • Clarifications if necessary: Do not try at home, bacteria or chemical
    • Not at all worked out for anything but tiny animals
    • Dose, effectiveness, timing, side effects
  • How does being in lab affect effect?
    • No comparison here of lab worms vs. wild-caught, or wild microbiota
    • Might not work the same in the wild
  • What do I think: Seems counterintuitive that knocking out genes in bacteria makes them helpful in extending life
    • Implies that bacteria were being harmful before, and then lost that ability?
    • Not quite; removing regulatory proteins that inhibit processes can give bacteria new powers
      • Like producing more colanic acid
  • Interesting interaction between bacteria and mitochondria
    • Mitochondria derived from intracellular bacteria long time ago
    • Possible that colanic acid plays some role between bacteria independent from host?
  • Lots of interesting questions to study
Last modified on Sunday, 17 December 2017 20:37
Jesse Noar

Jesse Noar is microbiologist with a PhD from North Carolina State University and Bachelor's from Cornell. Most of his research has focused on the amazing abilities and potential uses of bacteria, especially those found in soil. Jesse hosts the BacterioFiles podcast highlighting the most interesting recent microbiology research on all kinds of different microbes, part of the ASM family of podcasts. Learn more at asm.org/bacteriofiles or at www.bacteriofiles.com.

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