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BMS247 Stem Cells > L6 - Ageing and Sensecence > Flashcards

L6 - Ageing and Sensecence Flashcards

1
Q

What is sensecence

A

Age related decline in function

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2
Q

What are the posible reasons for senescence

A

Wear and tear

Genetics

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3
Q

Describe the evidence for the wear and tear model of sensence

A

Muscles thar are required for feeding degenerate over time because of their use

Elephants teeth wear away and they then die of starvation

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4
Q

What is the disposable soma thoery

A

Natural selection tunes life history of the organism so that sufficient rescources are invested in manitnianing repair mechanims AT LEAST UNTIL THEY HAVE TAKE CARE OF ITS YOUNG

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5
Q

Name three seescence factors

A

Metabolism
Reactive oxygen species
DNA damage

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6
Q

Factors which increase lifespan (3)

A

Dietary restriction
Environment
Signals from the somatic gonad

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7
Q

What is the rate of living theory

A

High metabolism gives a short lifespan –> larger animals live for longer

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8
Q

Why would cold blooded animals live for longer

A

Live at lower temperatures - don’t have to maintain a body temperature - lower rate of metabolism

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9
Q

High metabolism gives rise to

A

Reactive oxygen species (ROS)

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10
Q

What is central in the ROS theory of ageing

A

Superoxide radical `

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11
Q

What evidence is there to suggest that ROS radicals are anti-aging

A

In worms - paraquate of juglone treatment can act to increase the lifespan

Glucose restriction increases C.elegans lifespan by inducing mitochondrial respiration and increasing oxidative stress

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12
Q

Hutchinson guilford is caused by a mutation in what gene

What is the effect of this

A

LAMINA - affecting the nucelar architecture potentially impacting on the ability of the cell to repair DNA

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13
Q

Nestor Guillermo caused by mutations in what

A

BANF1 - affecting LAMINA and mitosis

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14
Q

Cockayne syndrome caused by

A

Muations in group 8 excision repair cross complementing proteins - affecting the ability to repair the DNA

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15
Q

How is Werners syndrome causes

A

Mutations in a RECQ helicase affecting repair/chromosomal segregation at anaphase

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16
Q

What is seen in mice with an increased rate of mutation

A

They do not age quicker

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17
Q

What type of DNA damage causes ageing

A

Unrepaired damage in non replicating cells

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18
Q

Why does unrepaired DNA damage in non-replicating cells cause aging

A

Through depletion of NDA through excessive PARP activation

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19
Q

What is PARP

A

Poly ADP ribose polyerase

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20
Q

What does PARP respond to

A

DNA damage

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21
Q

How many senescent cells promote the ageing phenotype

A

Through the secretion of pro-inflammaotry mediators

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22
Q

What is one factor which increases lifespan

A

Dietart restruction - lower nutrient metabolism (causes aging)

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23
Q

Describe howw the gerneration of ROS may increase lifespan

A

Low level of production may activate protective mechanims in a process called HORMESIS

24
Q

What is hormesis

A

Protective measures as a result of low level insults of ROS

25
Q

What else may increase lifespan

A

Emanation from the gonad (factors produced by the gomad)

26
Q

How may forward genetics be used to understanding ageing

A

Find mutants where aging is affected
Clone gene
Identify function

27
Q

Limitations of using short live mutants

A

Hard to tell which genes are required for ageing and which ones are required for life

28
Q

3 pathwyas involveing in ageing

A

IGF
TOR
Siryuins

29
Q

Normal c.elegans lifespan

A

25

30
Q

What is the max life span of C.elegans - how does it live this lng

A

Entering the dauer stage can live for 60 days and upwards

31
Q

What is the role of IGf

A

Inhibitions of DAF16 (AKA FOXO)

32
Q

DAF16 AKA

A

FOXO

33
Q

What is FOXO

A

A transcriptional regulator of genes which increase the resistance to various stressors

34
Q

What is the effect of mutations in the IGF pathway in flies

What does this do

A

Double lifespan

Puts flies into reproductive diapause

35
Q

What is the effect of mutating the IGF pathway in mammals

A

Can live for up to 3 times as long

36
Q

What type of genes does FOXO downregulate

A

Insulin like genes

Including :
Antioxidants 
Metabolic
Chaperones 
Antibacterial
37
Q

What is the role of FOXO on antioxidant genes

A

Increased resistance to ROS

38
Q

What is the role of FOXO downregulating antibacterial genes

A

Prevention of autophagy which limits lifespan

39
Q

What is TOR kinase

A

A major amino acid and nutrient sensor that stimulates gorwth and blocks slavage pathways such as autphagy when food is plentiful

40
Q

What is the effect of stress on the TOR pathway

A

Activation of TSC
Inhibition of TOR
Activation of 4E-BP and inhibition of S6K1

SALAVGE PATHWAYS ACTIVE

41
Q

What is the effect of growth factors and amino acids on TOR pathway

A

Blocking of TSC1-TSC2
Activation of Tor
Inactivation 4E-BP, activation of S6K1

WASTEFUL PATHWAYS ARE ACTIVE

42
Q

How does insulin interact with the TOR pathway

A

Growth factor that talks to TOR via PI3K and Akt causing the inactivation of TSC1/TSC2 and the activaiton of TOR

43
Q

Effect of blocking inuslin signalling

A

Inactivation of TOR

Activation of longevity pathways

44
Q

What is rapamycin

What are its effects

A

Blocking TOR

extends lifespan

45
Q

How is rapamycin seen to extend the life of OLD mice

A

Not through general reduction but through the reduction of life limitting factors (cancer)

46
Q

what are sirtuins

A

NAD dep ptoein deaceylases

47
Q

Affect of overexpression of sirtunins

A

Exntesion of lifespan

48
Q

What is the effect of Sir2.1 in C.elegans

A

Activation of FOXO/DAF16

Also UPR-mt

49
Q

What is UPR-mt

A

Mitochondrial unfolded protein response

50
Q

Sir proteins act as

A

Insulin dependent activatiors of Daf16/FOXO

51
Q

What is resveratrol

What does it activate

What is the knokc on result of this in mammals

A

Proposed anti-ageing agent in red win

Activation of Sir proteins

Downregulation of IGF1

52
Q

Sir pathway

A

NAD –> Sirtuins –> DAF16/FOXO + UPR-mt –> Longevity

53
Q

What is the NAD depeletion theory of aging

A

Certain mt mutations inc lifespan

Might cause a response of UPR-mt (like Sir)
NAD cofactor for sin - NAD levels decline with age

Unrepaired DNA damage may leaf to depletion of NAD and Poly ADP ribose polymerase (PARP) activation

54
Q

Describe what is seen in C elegans when

Removal of entire repro system

Removal of only germ cells

A

No effect

Animals live up to 60% longer

55
Q

Somatic gonad ____________ but these effects are __________ by the ______________

A

Extends

Counteracts

Germline

BMS247 Stem Cells (14 decks)

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