Ageing Flashcards
Senescence
Age related decline in function due to wear and tear and genetics
Disposable soma theory
as soon as the individual cannot increase the number or chance of survival of its offspring any further, there is no natural selection against decline/ageing in that individual
Senescence factors
metabolism
reactive oxygen species
DNA damage
Factors increasing life span
dietary restriction
environmental stresses
signals from the somatic gland
Rate of living theory
animals that have a higher metabolism have a shorter life span
large animals live longer and cold blood animals live longer at low temps
What are reactive oxygen species?
oxygen molecules that have an extra electron and are very reactive so will cause oxidative damage
superoxide radical is central to this
How is experimental data contradictory to the ROS theory?
in worms treatments that are superoxide dependent increased life span
glucose restriction increases life span in c’elegans by inducing mitochondrial repsiration and oxidative stress
resistance to oxidative stress is induced by longevity genes
How is DNA damage linked to ageing?
NAD depletion via excessive PARP activation
PARP is an enzyme that responds to damaged DNA
Hormesis
low level insults that may activate protective mechanisms
How do ROS levels contribute to ageing?
not an issue, they alert a cell to a problem to all activation of counter measures
high level of anti-oxidants means that ROS is suppressed and the alert is turned off
How can we use forward genetics to understand ageing?
find mutants that affect ageing and clone the gene to see what it does
search for short lived mutants
search for long lived mutants
IGF and TOR pathways
negative regulators of ageing, so when they are blocked life span is longer
Sirtuins
positive regulators of ageing so if over-active life span is longer
NAD+ dependent protein deacetylases
act as insulin dependent activators of daf16/foxo
What does insulin signalling block?
FOXO which is a TF that when in the nucleus, promotes anti-ageing functions and linked to resistance to oxidative stress
Antioxidant genes
superoxide dismutase
metakothionine
catalase
glutathionine
s-transferase
How are antibacterial genes implicated in ageing?
blockage of autophagy limits lifespan of long lived DAF2 and IGFR mutants
How are metabolic genes implicated in ageing?
apolipoprotein genes downregulated
glycoxylate-cycle genes
genes involved in amino acid turnover
TOR kinase
major amino acid and nutrient sensor that stimulates growth and blocks salvage pathways like autophagy when food is plentiful