Aging and senescence Flashcards
What is senescence?
What could this be due to?
Age related decline in function
Could be due the decline in stem cells during aging
How is senescence seen in drosophila?
What does this show?
Drosophila survival at 100% but rate of death rapidly increases with aging
Shows there is something limiting the lifespan
Is senescence due to wear and tear or genetics?
There is evidence for BOTH
What is the evidence of wear and tear for senscence?
1) Decline in muscle function in C.elegans
- Muscles for feeding degenerate over time as a result of their use –> unable to move/feed
2) Teeth worn off in elephants as they age –> die of starvation
What is the evidence of genetics for senscence?
1) Salmon
- Die soon after laying their eggs
2) Species differences in aging:
- Gestation period of elephant is 21 months
- Life span of mouse is 42months (within 21 months –> already shows clear signs of aging)
- Genetic programme in how different animals age
What theory explains aging?
The disposable soma theory:
- Natural selection tunes the life history of the organism so that sufficient resources are invested in maintaining the repair mechanisms that prevents aging
- At least until the organism has reproduced and cared for its young
- As soon as an individual cannot increase the number, or chance of survival of its offspring any further - there is no natural selection against decline/aging
If there are genes/mechanisms that increase the chance of reproductive success, what happens to them over life?
These genes are present in early life but contribute to killing the organism when the progeny is independant
Act to kill off animals that can’t help their offspring any further
What are 3 senescence factors?
1) Metabolism
2) Reactive oxygen species
3) DNA damage
What is the rate of living theory?
Examples
States that HIGH METABOLISM –> SHORT LIFESPAN
- Low metabolism in larger animals –> live longer
- Cold blooded animals live longer at LOWER temperatures
What happens in species with a high metabolism?
What does this cause?
Generate a reactive oxygen species (ROS):
- Superoxide which has a free electron, which is very reactive and unstable
- -> Causes OXIDATIVE DAMAGE to many molecules in the animal
What is the superoxide radical produced in an animal with a high metabolism central to?
Central to the ROS theory of aging
What are the contradictory results when manipulating ROS?
1) When treat WORMS with known oxygen species generators –> INCREASE lifespan
- If take out the superoxide anion –> shorten lifespan
2) Glucose restriction extends the life of C.elegans by inducing mitochondiral respiration and INCREASING oxidative stress
3) Some genes increase the RESISTANCE to oxidative stress and give longevity to animals
What are some of the ideas about how ROS works to increase/decrease lifespan?
1) May be another form of molecular damage related to oxygen that causes damage
2) May be due to the LEVELS of ROS - able to cope with levels in the body but if increase –> alarm system
What are progeria sydromes?
What is the cause?
Premature aging
Genetic cause - likely to be driving aging or preventing aging under normal conditions
What are examples of progeria sydromes?
1) Hutchinson Guilford
2) Nestor Guillermo
3) Ehlers Danos
4) Cockayne
5) Werner
What is aging to do with?
Nuclei/DNA/DNA repair
What is the DNA damage theory of aging?
States that DNA damage is the reason for aging:
- In non-replicating cells, unrepaired/unrepairable DNA damage may ACCUMULATE and cause aging
What happens to unrepaired DNA in dividing cells?
Will lead to mutations
Why do mice with a high mutation rate NOT age quicker?
It is the UNREPAIRED DNA damage that causes aging
NOT the mutation itself
Why is it likely that unrepaired DNA damage is likely to cause aging?
NAD depletion? PARP activation?
- Un repaired DNA leads to the activation of an enzyme PARP
- PARP normally uses NAD and responds to DNA damage –> depleting NAD
- Lots of un repaired DNA damage –> lots of PARP and lack of NAD
–> may cause senescence (age related decline in function)
What is PARP?
Poly ADP-ribose polymerase
How may senescent cell drive the important aspects of aging?
- Lots of DNA damage but don’t die
1) Have a senescence-associated secretory phenotype (SASP):
- Secrete molecules that ATTRACT and ACTIVATE IMMUNE cells –> leading to INFLAMMATION
2) Block stem cell mediated repair:
- Sit in the stem cell niche and ‘hog’ the space –> preventing GOOD stem cells from developing and doing their job
What happened in mice when removed the senescent cells?
They didn’t age as much as the mouse that still had them
What are 3 factors that increase life span?
1) Dietary restriction
2) Environmental stresses
3) Signals from the somatic gonad
In what organisms does dietary restriction increase lifespan?
In ALL model organisms