BacterioFiles 321 - Escherichia Extends elegans Existence

Caenorhabditis elegans
By Bob Goldstein, UNC Chapel Hill
CC BY-SA 3.0

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

Download Episode (9.9 MB, 10.75 minutes)

Show notes:
News 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