Wk.4 L3 - Pathways that control Longevity

Question 1

LO

Answer 1

• Explain key functions of the insulin signalling pathway
• Describe how insulin/IGF-1 signalling can control gene expression
• Explain the roles different model organisms can have in longevity studies
• Outline the effects of the insulin/IGF-1signalling and mTOR pathways on longevity

Question 2

Insulin

Answer 2

Made in pancreatic islet beta cells
Respond to food intake, carbohydtates -> Glucose -> Secretion of Insulin

WAT, Muscle and liver uptake glucose

Question 3

Insulin signalling and Transcriptional effects

Answer 3

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Insulin inhibits FOXO by causing it to be phosphorylated. Stopping the liver from producing glucose

FOXO is a transcription factor:
- Goes into nucleus to regulate transcription of certain genes

Question 4

Animal models of lifespan research

Answer 4

Non-human primate and Large animal models:
- Relevance to human physiology

Rodent and non-mammalian models:
- Throughput same pathways but shorter lifespans

Hard to do lifespan research on humans, so we use animal models

Question 5

Insulin/ IGF-1 Signalling

Answer 5

It is conserved by the body
- High insulin signalling is bad for longevity

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Question 6

Insulin-like Growth Factor 1 (IGF-1)

Answer 6

Controls growth and body size in mammals
- Insulin controls metabolism
- IGF-1 controls body growth

In dogs:
- Smalls dogs have a mutation on IGF-1 gene that changes the transcription and therfore also translation and production of IGF-1
- Bigger dogs have bigger IGF-1 genes

More IGF-1 signalling = less FOXO activity (therefore shorter lifespan)

Question 7

mTOR Signalling

Answer 7

mTOR Activators:
- Leucine (Amino Acid)
- Arginine (Amino Acid)
- Active Akt

Rapamycine inhibits mTOR signalling, evidently extending the lifespan of mice.

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