Drosophila as a model for ageing Flashcards
What is ageing?
A progressive, irreversible decline in organismal perfomance
Which main factors influence ageing?
Genetics- at birth including mutations accumulated with age
Envrionment- diet, lifestyle, exposure to various external factors
Who do we like to study c.elegans and drosophila?
Short average lifespans
Easy to culture- small
Genetically tractable
Controllable environment
How do we measure ageing?
We look at the age of death
plot them on a survival curve
look at the median lifespan
What is the median lifespan?
the number of days at which 50% of the population is still alive
What is a key pathway in ageing?
Insulin/ IGF pathway
What is characteristic of chico mutants?
Longer medial lifespan ‘long lived mutants’
What does an increase in FOXO and a decrease in insulin signalling cause?
Increased autophagy
Increased DNA repair
Decreased oxidative stress
= Increase in life longevity
What gene triggers insulin response in response to nutrients? (in drosophila) What occurs in mutants of this gene?
Methuselah
Mutants are long lived
What does the agonist of methuselah do?
Peptide antagonist extends lifespan
but DOES not increase healthy living
How does dietary restriction affect lifespan?
Modest D.R increases lifespan
Is dietary restriction required throughout life to have its effects?
NO
D.R decreases the probability of death from the point of restriction
What are 3 characteristics of Alzheimers disease?
- Neuronal cell death
- Tissue atrophies
- Accumulation of beta amyloid peptide
How can we overexpress a gene in drosophila?
UAS/GAL4 system
one fly- GAL4 dowstream of a native promoter- specific to the tissue of interest
other fly- UAS placed upstream of the target gene
cross breed
GAL4 acts on UAS to transcribe the gene of interest
single transgenic fly overexpresses the gene of interest
How was overexpression studies been used in drosophila to aid Alzheimers research?
overexpressed beta amyloid (which is neurotoxic to them)
induced mutations in the flies-
screened for mutations which increased lifespan following overexpression of the toxic protein
What was found to increase lifespan in the beta-amyloid mutant flies?
IDE- insulin degrading enzyme
increased lifespan and reduced neurotoxicity induced by the protein
Components of the mammalian insulin pathway- how similiar is it to drosophila?
IRS->PI3K->PDK1->AKT/PKB/SGK-| FOXO1-> longevity genes
CHICO is analgous to IRS
everything from PI3K onwards is the same in drosophila- but just FOXO
What does increased expression of FOXO cause in flies?
Extension of lifespan
What does insulin signalling = in terms of ageing?
Decreased lifespan
