Lessons from Model Organisms

Question 1

What are the advantages of Saccharomyces cerevisae (yeast) as a model organism?

Answer 1

Cheap

Best genetics

Question 2

What is a disadvantage of Saccharomyces cerevisae (yeast) as a model organism?

Answer 2

Unicellular fungus - may not age in same way as animal

Question 3

What are the advantages of Caenorhabditis elegans as a model organism?

Answer 3

Cheap
Shows real ageing
Short lifespan - fast experiments
No inbreeding effects

Question 4

What is a disadvantage of Caenorhabditis elegans as a model organism?

Answer 4

Not mammal - findings may not apply to humans

Question 5

What are the advantages of Drosophila melanogaster as a model organism?

Answer 5

Short lifespan - fast experiments

Organ complexity and genes closer to mammals than in C. elegans

Question 6

What are the disadvantages of Drosophila melanogaster as a model organism?

Answer 6

Inbreeding effects

More expensive than C. elegans

Question 7

What are the advantages of Mus musculus as a model organism?

Answer 7

Mammal

Good genetics

Question 8

What are the disadvantages of Mus musculus as a model organism?

Answer 8

Long lifespan - slow experiments

Very expensive

Question 9

What are inbreeding effects?

Answer 9

Inbreeding increases homozygosity for recessive mutations that shorten lifespan in population
Confounding variable in lifespan studies

Question 10

Is ageing monogenic or polygenic?

Answer 10

Polygenic

Question 11

What type of protein does Target of Rapamycin (TOR) encode?

Answer 11

Protein kinase

Question 12

Name the mammalian TOR complexes

Answer 12

mTORC1

mTORC2

Question 13

What is the effect of rapamycin?

Answer 13

Inhibits mTOR

Question 14

How does long-term mTORC1 inhibition affect mTORC2 activity?

Answer 14

Indirectly

Question 15

When are mTORC1 and mTORC2 activated?

Answer 15

Under favourable conditions

Question 16

What does mTORC1 respond to?

Answer 16

Growth factors

O2

Question 17

What is the effect of mTORC1 activation?

Answer 17

Increased protein synthesis, decreased autophagy - cell growth

Question 18

What does mTORC2 respond to?

Answer 18

Growth factors

Question 19

What is the effect of mTORC2 activation?

Answer 19

Increased survival and proliferation

Question 20

What is the overall effect of TORC1 inhibition?

Answer 20

Lifespan extension

Question 21

Define replicative lifespan

Answer 21

Capacity of cell to produce progeny

Question 22

Define chronological lifespan

Answer 22

Capacity of cell to survive in quiescence

Question 23

What is the effect of TOR1 KO in yeast?

Answer 23

Increases replicative and chronological lifespan

Question 24

How does RNAi work?

Answer 24

Short RNAs guide RISC complex to target mRNA - cleaves - prevents translation

Question 25

Why might the lifespan extension have been larger in TOR KO C. elegans than in TOR RNAi?

Answer 25

RNAi given after development - some TOR protein made early | RNAi has lower efficiency at preventing protein formation than KO - partial gene inhibition

Question 26

How does the GAL4/UAS binary transgenic system work?

Answer 26

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

Question 27

What is the effect of using GAL4/UAS to express a TOR inhibitor in a single tissue in Drosophila?

Answer 27

Increases lifespan

Question 28

What is the effect of a heterozygous mTOR KO in mice?

Answer 28

Increases lifespan

Question 29

What are the roles of TORC1?

Answer 29

Translation regulation Metabolism Protein turnover - blocks autophagy and proteasome assembly

Question 30

What does the translation regulation role of TORC1 support?

Answer 30

Gene hyperfunction theory

Question 31

What does the protein turnover role of TORC1 support?

Answer 31

Damage/maintenance theory

Question 32

What is the effect of TORC1 inhibition in multiple species?

Answer 32

Increases lifespan

Question 33

How does TORC1 inhibition increase lifespan?

Answer 33

Unknown | Probably due to effects on multiple pathways