Lecture 31 Flashcards
What is meant by senescence
The age-related decline in physiological function
Give examples of wear senescence is characterised by wear and tear
In C.elegans there is a decline in muscle function which prevents eating and ultimately leads to death. The same is true in elephants where the teeth are worn down and the animal starves
Other than wear and tear what other mechanism has been proposed to explain the course of aging
It is part of a genetic program
What is meant by the disposable soma theory
Once an individual cannot increase its species number or the chance of survival of its offspring, there is no natural selection against decline/aging
Genes/mechanisms that increase the reproductive success in early life stages but are deleterious once progeny are independent will still be selected for, T or F
T
What are the main factors proposed for aging
ROS, metabolism and DNA damage
Explain the rate of living theory
A high metabolism results in a shorter lifespan and larger animals live longer
Cold blooded animals live longer at high temperatures, T or F
F – they live longer at lower temperatures
A high metabolism can also link into one of the other factors seen in aging. Explain how this occurs
A high metabolism leads to the formation of ROS which can cause increased oxidative damage
Explain how data contradicts the proposed ROS theory of aging
Introducing factors that increase ROS generation lead to increased lifespan in mice models. However this longevity is proposed to be due to the induction of anti-oxidant genes
Explain the DNA damage theory of aging in contrast to mutations
In non-replicating cells, unrepaired/able DNA damage may accumulate and cause aging. Whereas, in dividing cells unrepairable DNA damage will lead to mutations
What are the effects of dietary restriction on the aging process
Limiting the amount of food an animal can have over time, increases its lifespan by a mechanism not entirely related to metabolism
Other environmental stressors such as heat and ROS generators have been found to influence aging. Explain the idea that these stresses cause hormesis
These environmental stressors can be thought of as low level insults to the organism. These low level insults may activate protective mechanisms that outperform the initial insult
Why is it that forward genetics looking to identify mutants with enhanced aging not very effective
Due to the vast number of different genes involved in cell death
Why is it that forward genetic screens looking for long living mutants isn’t feasible in vertebrates
Due to their long lifespan limiting the time taken to investigate long living mutants
Which model systems are often used to identify long living mutants
Developmental models such as Drosophila and C.elegans
Which three classes of genes have been determined to play a role in ageing
IGF pathway, TOR pathway and sirtuins
What is the dauer stage in C.elegans and what is its significance in aging
The dauer stage happens when C.elegans encounter stresses like crowding or low food availability. It causes them to enter an extra stage in their lifespan that can last for up to 60 days where the IGF pathway is particularly important
Explain the role of the IGF signalling pathway in aging
The IGF signalling pathway is a life-limiting one and as such, inactivation of the pathway can actually extend life
Mutations in the insulin-like growth factor pathway can extend lifespans, T or F
T
Explain the role of DAF2 in IGF signalling
DAF2 is a type of IGFR and signalling via this pathway inhibits the activity of DAF16 or FOXO in humans as well as SKN1 and HSF1
List some of the downstream targets of DAF16/FOXO
Antioxidant genes, metabolic genes, chaperones and antibacterial genes
Lifespan extension by dietary restriction is mostly or partly mediated by IGF signalling, T or F
T
What is the role of the TOR pathway in aging
TOR kinase is a major amino-acid and nutrient sensor. It stimulates growth and blocks salvage pathways such as autophagy when food is plentiful. Inhibition of TOR signalling increases lifespan
What are sirtuins
NAD+ dependant protein deacetylases
What is the link between sirtuins and aging
Overexpression of sirtuins in yeast, worms and flies has been shown to increase lifespan
What is the name of the proposed anti-aging compound found in red wine and in Japanese Knotweed that has been found to activate Sir proteins
Resveratrol
Decline in NAD levels have also been linked with aging, T or F
T
Somatic gonads extend lifespan but their effects are counteracted by the germ line, T or F
T
Removal of the entire reproductive system from C.elegans has been shown to increase their lifespan, T or F
F – however, when only germ cells are removed animals live 60% longer
