Aging

Question 1

Aging can be a result of what two things - give examples in organisms

Answer 1

‘wear and tear’ - decline in muscle function in drosophila or teeth worn down in elephants
Genetic - eg salmon die after they lay their eggs

Question 2

What are the differences in aging between elephants and mice?

Answer 2

Mice live for only 41 months

By the time an elephant is born (gestation = 21 months) a mouse is half way through their life

Question 3

What is the disposable soma theory?

Answer 3

Natural selection tunes life history of the organism so that sufficient resources are invested in maintaining the repair mechanisms that prevent aging at least until the organism has reproduced and cared for its young

Question 4

List three senescence factors

Answer 4

DNA damage
Reactive oxygen species
Metabolism

Question 5

Give three factors which increase life span

Answer 5

Dietry restriction
Enviromental stress
Signals from the somatic gonad

Question 6

What is the rate of living theory?

Answer 6

Higher metabolism means organisms have a shorter life span
ie larger animals will live longer
whales = 200 years
flies = 150 days

Question 7

How can drosophila show that a slower metabolism means organisms live longer?

Answer 7

Flies kept at 18 degress will live longer than those living at 29 degrees
18 = 120 days
29 = 40 days

Question 8

Metabolism is a source of what?

Answer 8

Reactive oxygen species

Question 9

What happens in worms treated with paraquol or juglone?

Answer 9

They have a longer life span showing they could be superoxide dependent
Contradicts the theory

Question 10

How does glucose restriction increase lifespan?

Answer 10

It induces mitochondrial respiration increasing oxidative stress

Question 11

Resistance to oxidative stress is induced by what?

Answer 11

Longevity genes

Question 12

List some types of progeria syndromes

Answer 12

Hutchinson Guilford
Nestor Guillermo
Ehlers Danos
Cokayne
Werner

Question 13

What is progeria?

Answer 13

Premature aging

Question 14

What is hutchinson guilford disease?

Answer 14

A lamina mutation = nuclear architecture DNA repair

Question 15

What is nestor Guillermo?

Answer 15

BANF1 mutation = lamina/mitosis

Question 16

What is Ehlers Danos a mutation in?

Answer 16

Xylosylprotein 4-beta-galactosyltransferase

Question 17

What is cockayne?

Answer 17

Group 8 excision repair cross complementing protein = DNA repair

Question 18

In a non replicating cell DNA damage will cause what?

Answer 18

Aging = senescence

Question 19

Do mice with higher mutations age quicker?

Answer 19

No

This suggests that damage causes aging in cells

Question 20

What is PARP?

Answer 20

An enzyme essential for certain DNA repair processes

Question 21

What happens in mice which are genetically reprogrammed to destroy senescent cells?

Answer 21

They live longer

Question 22

What is hormesis?

Answer 22

When an enviromental stress activates protective mechanisms

A small insult can unleash a disproportionate protective response

Question 23

When using forward genetics to identify genes involved in ages what phenotype is looked for and why?

Answer 23

Animals that live longer

Those that live shorter could be due to a variety of mechanisms and so may not be directly linked to aginf

Question 24

The use of genetics identified which three pathways involved in aging?

Answer 24

IGF
TOR
Sirtuins

Question 25

If L1 C.elegans are put in adverse conditions what happens?

Answer 25

They enter the dauer state which increases their life span from 25 to 60 days
This is under IGF1 control

Question 26

Genetic screens have identified mutants which promoting longevity. What is their effect on the IGF pathway?

Answer 26

They were found to block insulin signalling

Question 27

In drosophila the loss of IGF has been linked to what?

Answer 27

Resistace to oxidative stress

Question 28

Female mice with mutations in IGF receptors 1 and 2 can live for how long?

Answer 28

Up to 33% longer than a normal mouse

Question 29

Which receptor variants have been linked to human longevity in multiple cohort studies?

Answer 29

FOXO1, FOXO3A, AKT and IGF1

Question 30

Lifespan extension by dietry restricton is mediated by what?

Answer 30

IGF signalling

Question 31

Which genes are downstream of DAF16/FOXO in c.elegans?

Answer 31

Antiooxidant genes
Metabolic genes
Chaperones
Antibacterial genes

Question 32

What is TOR kinase?

Answer 32

A major amino acid and nurtrient sensor

Stimulates growth and blocks salvage pathways such as autophagy when food is plentiful

Question 33

How is the salvage pathway activated?

Answer 33

In times of stress

Activates TSC which blocks TOR so 4E-BP4 is activates and S6KI is blocked so no cell growth or protein synthesis occurs

Question 34

What is the effect of growth factors on the TOR pathway?

Answer 34

They block TSC1 -TSC2 so TOR is active
4E-BP4 is blocked
S6KI is active so the wasteful pathway is active

Question 35

Insulin talks to the TOR pathway via what?

Answer 35

PI3K and Akt

Question 36

What is rapamycin?

Answer 36

Extends the life span of old mice
May be due to general reduction in aging phenotypes eg cancer rather than a reduction of a subset of important life limiting factors

Question 37

Sirtuins are the target of what in red wine?

Answer 37

Resveratrol

Question 38

Overexpression of sirtuins leads to what?

Answer 38

Extended lifespan in yeast, worms and flies

Question 39

What is the effect of sirtuins which leads to longevity?

Answer 39

DAF16/FOXO are activated

Mitochondrial unfolded protein response

Question 40

What happens in c.elegans when you remove the reproductive system vs the germ cells

Answer 40

Removal of reproductive system does not extend the lifespan

Removal of the germ line extends the life span up to 60%