Aging Flashcards

1
Q

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

A

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

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2
Q

What are the differences in aging between elephants and mice?

A

Mice live for only 41 months

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

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3
Q

What is the disposable soma theory?

A

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

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4
Q

List three senescence factors

A

DNA damage
Reactive oxygen species
Metabolism

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5
Q

Give three factors which increase life span

A

Dietry restriction
Enviromental stress
Signals from the somatic gonad

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6
Q

What is the rate of living theory?

A

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

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7
Q

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

A

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

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8
Q

Metabolism is a source of what?

A

Reactive oxygen species

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9
Q

What happens in worms treated with paraquol or juglone?

A

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

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10
Q

How does glucose restriction increase lifespan?

A

It induces mitochondrial respiration increasing oxidative stress

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11
Q

Resistance to oxidative stress is induced by what?

A

Longevity genes

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12
Q

List some types of progeria syndromes

A
Hutchinson Guilford
Nestor Guillermo
Ehlers Danos
Cokayne
Werner
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13
Q

What is progeria?

A

Premature aging

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14
Q

What is hutchinson guilford disease?

A

A lamina mutation = nuclear architecture DNA repair

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15
Q

What is nestor Guillermo?

A

BANF1 mutation = lamina/mitosis

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16
Q

What is Ehlers Danos a mutation in?

A

Xylosylprotein 4-beta-galactosyltransferase

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17
Q

What is cockayne?

A

Group 8 excision repair cross complementing protein = DNA repair

18
Q

In a non replicating cell DNA damage will cause what?

A

Aging = senescence

19
Q

Do mice with higher mutations age quicker?

A

No

This suggests that damage causes aging in cells

20
Q

What is PARP?

A

An enzyme essential for certain DNA repair processes

21
Q

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

A

They live longer

22
Q

What is hormesis?

A

When an enviromental stress activates protective mechanisms

A small insult can unleash a disproportionate protective response

23
Q

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

A

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

24
Q

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

A

IGF
TOR
Sirtuins

25
If L1 C.elegans are put in adverse conditions what happens?
They enter the dauer state which increases their life span from 25 to 60 days This is under IGF1 control
26
Genetic screens have identified mutants which promoting longevity. What is their effect on the IGF pathway?
They were found to block insulin signalling
27
In drosophila the loss of IGF has been linked to what?
Resistace to oxidative stress
28
Female mice with mutations in IGF receptors 1 and 2 can live for how long?
Up to 33% longer than a normal mouse
29
Which receptor variants have been linked to human longevity in multiple cohort studies?
FOXO1, FOXO3A, AKT and IGF1
30
Lifespan extension by dietry restricton is mediated by what?
IGF signalling
31
Which genes are downstream of DAF16/FOXO in c.elegans?
Antiooxidant genes Metabolic genes Chaperones Antibacterial genes
32
What is TOR kinase?
A major amino acid and nurtrient sensor | Stimulates growth and blocks salvage pathways such as autophagy when food is plentiful
33
How is the salvage pathway activated?
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
34
What is the effect of growth factors on the TOR pathway?
They block TSC1 -TSC2 so TOR is active 4E-BP4 is blocked S6KI is active so the wasteful pathway is active
35
Insulin talks to the TOR pathway via what?
PI3K and Akt
36
What is rapamycin?
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
37
Sirtuins are the target of what in red wine?
Resveratrol
38
Overexpression of sirtuins leads to what?
Extended lifespan in yeast, worms and flies
39
What is the effect of sirtuins which leads to longevity?
DAF16/FOXO are activated | Mitochondrial unfolded protein response
40
What happens in c.elegans when you remove the reproductive system vs the germ cells
Removal of reproductive system does not extend the lifespan | Removal of the germ line extends the life span up to 60%