Lessons from Model Organisms Flashcards
What are the advantages of Saccharomyces cerevisae (yeast) as a model organism?
Cheap
Best genetics
What is a disadvantage of Saccharomyces cerevisae (yeast) as a model organism?
Unicellular fungus - may not age in same way as animal
What are the advantages of Caenorhabditis elegans as a model organism?
Cheap
Shows real ageing
Short lifespan - fast experiments
No inbreeding effects
What is a disadvantage of Caenorhabditis elegans as a model organism?
Not mammal - findings may not apply to humans
What are the advantages of Drosophila melanogaster as a model organism?
Short lifespan - fast experiments
Organ complexity and genes closer to mammals than in C. elegans
What are the disadvantages of Drosophila melanogaster as a model organism?
Inbreeding effects
More expensive than C. elegans
What are the advantages of Mus musculus as a model organism?
Mammal
Good genetics
What are the disadvantages of Mus musculus as a model organism?
Long lifespan - slow experiments
Very expensive
What are inbreeding effects?
Inbreeding increases homozygosity for recessive mutations that shorten lifespan in population
Confounding variable in lifespan studies
Is ageing monogenic or polygenic?
Polygenic
What type of protein does Target of Rapamycin (TOR) encode?
Protein kinase
Name the mammalian TOR complexes
mTORC1
mTORC2
What is the effect of rapamycin?
Inhibits mTOR
How does long-term mTORC1 inhibition affect mTORC2 activity?
Indirectly
When are mTORC1 and mTORC2 activated?
Under favourable conditions
What does mTORC1 respond to?
Growth factors
O2
What is the effect of mTORC1 activation?
Increased protein synthesis, decreased autophagy - cell growth
What does mTORC2 respond to?
Growth factors
What is the effect of mTORC2 activation?
Increased survival and proliferation
What is the overall effect of TORC1 inhibition?
Lifespan extension
Define replicative lifespan
Capacity of cell to produce progeny
Define chronological lifespan
Capacity of cell to survive in quiescence
What is the effect of TOR1 KO in yeast?
Increases replicative and chronological lifespan
How does RNAi work?
Short RNAs guide RISC complex to target mRNA - cleaves - prevents translation
Why might the lifespan extension have been larger in TOR KO C. elegans than in TOR RNAi?
RNAi given after development - some TOR protein made early
RNAi has lower efficiency at preventing protein formation than KO - partial gene inhibition
How does the GAL4/UAS binary transgenic system work?
One line with GAL4 transcription factor - under tissue-specific promoter
One line with transgene - under promoter containing UAS sequences
In progeny - transgene only expressed in cells expressing GAL4 - tissue-specific transgene expression
What is the effect of using GAL4/UAS to express a TOR inhibitor in a single tissue in Drosophila?
Increases lifespan
What is the effect of a heterozygous mTOR KO in mice?
Increases lifespan
What are the roles of TORC1?
Translation regulation
Metabolism
Protein turnover - blocks autophagy and proteasome assembly
What does the translation regulation role of TORC1 support?
Gene hyperfunction theory
What does the protein turnover role of TORC1 support?
Damage/maintenance theory
What is the effect of TORC1 inhibition in multiple species?
Increases lifespan
How does TORC1 inhibition increase lifespan?
Unknown
Probably due to effects on multiple pathways
