drosophila ageing Flashcards
what is ageing?
the progressive irreversible decline in an organsims performance
what is the maximum human lifespan?
125 years
122 years - oldest proven human
what factors can influence ageing?
genetics - genotype at birth + cumulative mutations
environment - e.g. diet, smoking, drigs, alcohol, external factors
What experimental approaches are used to measure ageing?
- is no direct way to measure ageing - only an estimate
- measure age of death
- median lifespan often used
- use large cohort of animals and compare proportion alive
what makes drospophila a good model organsim to demonstarte ageing?
- genome sequenced
- some conserved genes
- short lifespan
- genetic screens can be carried out
- large population sizes
what happens in drosophila chico mutants (chico LOF)
- chico LOF mutants increase drosophila lifespan
- 36% increase in heterozygotes (females) and 48% increase in homozygotes (female)
- less effective in males
- is an insulin receptor substrate
- chico 1 decrease - insulin like pathway decrease - life span increase
what effect does reduced insulin signalling have?
-increased life span
what pathway causes insulin signalling reduction to result in longevity?
- insulin/ IGF/ mTOR decrease
- foxo increase
- increase in autophagy and DNA repair, decrease in oxidative stress
- health and longevity
what gene mutations in c.elegans cause longevity?
-Daf-2 and age-1 mutations LOF
(encode components of the insulin - like - pthway)
- increases lifespan by 200%
what effect does dietary restirction have on lifespan?
- modest dietary restriction increases lifespan
- too little food-starvation - early death, too much food- early death
- more effective in females
- dietary restriction causes increase in median lifespan and causes shift in survivial
is dietary restriciton required throughout life to increasse lifespan?
no
- dietary restriciton at any point can increase lifespan/reduce risk of death
- if dietary restrciton stopped at any point - risk of death increases to normal full fed diet
what is CALORIE?
comprehensive assessment of long-term effects of reducing intake of energie
(studies in humans to see if dietary restriction works )
how does dietary restriction increase lifespan?
- decreases circulating insulin levels (increases FOXO) - increases autophagy, DNA repair and reduces pxodative stress
- less apidosity - less risk of CV disease
- less inflammation - less risk of cancer
- increase hsf and hsp70 - increase autophagy and DNA repair
what is the average age of death in the UK population?
in 1960 - 71
in 2010 - 80
- ageing population increasing
- age is risk factor associated with many diseases. e.g. alzheimers, cancer, heart problems
how is alzheimers caused?
- accumulation of B amyloid peptides/plaques - these are neurotoxic
- neurodegeneration due to death of neurons
