Lecture 31

Question 1

What is meant by senescence

Answer 1

The age-related decline in physiological function

Question 2

Give examples of wear senescence is characterised by wear and tear

Answer 2

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

Question 3

Other than wear and tear what other mechanism has been proposed to explain the course of aging

Answer 3

It is part of a genetic program

Question 4

What is meant by the disposable soma theory

Answer 4

Once an individual cannot increase its species number or the chance of survival of its offspring, there is no natural selection against decline/aging

Question 5

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

Answer 5

T

Question 6

What are the main factors proposed for aging

Answer 6

ROS, metabolism and DNA damage

Question 7

Explain the rate of living theory

Answer 7

A high metabolism results in a shorter lifespan and larger animals live longer

Question 8

Cold blooded animals live longer at high temperatures, T or F

Answer 8

F – they live longer at lower temperatures

Question 9

A high metabolism can also link into one of the other factors seen in aging. Explain how this occurs

Answer 9

A high metabolism leads to the formation of ROS which can cause increased oxidative damage

Question 10

Explain how data contradicts the proposed ROS theory of aging

Answer 10

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

Question 11

Explain the DNA damage theory of aging in contrast to mutations

Answer 11

In non-replicating cells, unrepaired/able DNA damage may accumulate and cause aging. Whereas, in dividing cells unrepairable DNA damage will lead to mutations

Question 12

What are the effects of dietary restriction on the aging process

Answer 12

Limiting the amount of food an animal can have over time, increases its lifespan by a mechanism not entirely related to metabolism

Question 13

Other environmental stressors such as heat and ROS generators have been found to influence aging. Explain the idea that these stresses cause hormesis

Answer 13

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

Question 14

Why is it that forward genetics looking to identify mutants with enhanced aging not very effective

Answer 14

Due to the vast number of different genes involved in cell death

Question 15

Why is it that forward genetic screens looking for long living mutants isn’t feasible in vertebrates

Answer 15

Due to their long lifespan limiting the time taken to investigate long living mutants

Question 16

Which model systems are often used to identify long living mutants

Answer 16

Developmental models such as Drosophila and C.elegans

Question 17

Which three classes of genes have been determined to play a role in ageing

Answer 17

IGF pathway, TOR pathway and sirtuins

Question 18

What is the dauer stage in C.elegans and what is its significance in aging

Answer 18

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

Question 19

Explain the role of the IGF signalling pathway in aging

Answer 19

The IGF signalling pathway is a life-limiting one and as such, inactivation of the pathway can actually extend life

Question 20

Mutations in the insulin-like growth factor pathway can extend lifespans, T or F

Answer 20

T

Question 21

Explain the role of DAF2 in IGF signalling

Answer 21

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

Question 22

List some of the downstream targets of DAF16/FOXO

Answer 22

Antioxidant genes, metabolic genes, chaperones and antibacterial genes

Question 23

Lifespan extension by dietary restriction is mostly or partly mediated by IGF signalling, T or F

Answer 23

T

Question 24

What is the role of the TOR pathway in aging

Answer 24

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

Question 25

What are sirtuins

Answer 25

NAD+ dependant protein deacetylases

Question 26

What is the link between sirtuins and aging

Answer 26

Overexpression of sirtuins in yeast, worms and flies has been shown to increase lifespan

Question 27

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

Answer 27

Resveratrol

Question 28

Decline in NAD levels have also been linked with aging, T or F

Answer 28

T

Question 29

Somatic gonads extend lifespan but their effects are counteracted by the germ line, T or F

Answer 29

T

Question 30

Removal of the entire reproductive system from C.elegans has been shown to increase their lifespan, T or F

Answer 30

F – however, when only germ cells are removed animals live 60% longer