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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
What else may increase lifespan
Emanation from the gonad (factors produced by the gomad)
26
How may forward genetics be used to understanding ageing
Find mutants where aging is affected Clone gene Identify function
27
Limitations of using short live mutants
Hard to tell which genes are required for ageing and which ones are required for life
28
3 pathwyas involveing in ageing
IGF TOR Siryuins
29
Normal c.elegans lifespan
25
30
What is the max life span of C.elegans - how does it live this lng
Entering the dauer stage can live for 60 days and upwards
31
What is the role of IGf
Inhibitions of DAF16 (AKA FOXO)
32
DAF16 AKA
FOXO
33
What is FOXO
A transcriptional regulator of genes which increase the resistance to various stressors
34
What is the effect of mutations in the IGF pathway in flies What does this do
Double lifespan Puts flies into reproductive diapause
35
What is the effect of mutating the IGF pathway in mammals
Can live for up to 3 times as long
36
What type of genes does FOXO downregulate
Insulin like genes ``` Including : Antioxidants Metabolic Chaperones Antibacterial ```
37
What is the role of FOXO on antioxidant genes
Increased resistance to ROS
38
What is the role of FOXO downregulating antibacterial genes
Prevention of autophagy which limits lifespan
39
What is TOR kinase
A major amino acid and nutrient sensor that stimulates gorwth and blocks slavage pathways such as autphagy when food is plentiful
40
What is the effect of stress on the TOR pathway
Activation of TSC Inhibition of TOR Activation of 4E-BP and inhibition of S6K1 SALAVGE PATHWAYS ACTIVE
41
What is the effect of growth factors and amino acids on TOR pathway
Blocking of TSC1-TSC2 Activation of Tor Inactivation 4E-BP, activation of S6K1 WASTEFUL PATHWAYS ARE ACTIVE
42
How does insulin interact with the TOR pathway
Growth factor that talks to TOR via PI3K and Akt causing the inactivation of TSC1/TSC2 and the activaiton of TOR
43
Effect of blocking inuslin signalling
Inactivation of TOR | Activation of longevity pathways
44
What is rapamycin What are its effects
Blocking TOR extends lifespan
45
How is rapamycin seen to extend the life of OLD mice
Not through general reduction but through the reduction of life limitting factors (cancer)
46
what are sirtuins
NAD dep ptoein deaceylases
47
Affect of overexpression of sirtunins
Exntesion of lifespan
48
What is the effect of Sir2.1 in C.elegans
Activation of FOXO/DAF16 Also UPR-mt
49
What is UPR-mt
Mitochondrial unfolded protein response
50
Sir proteins act as
Insulin dependent activatiors of Daf16/FOXO
51
What is resveratrol What does it activate What is the knokc on result of this in mammals
Proposed anti-ageing agent in red win Activation of Sir proteins Downregulation of IGF1
52
Sir pathway
NAD --> Sirtuins --> DAF16/FOXO + UPR-mt --> Longevity
53
What is the NAD depeletion theory of aging
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
Describe what is seen in C elegans when Removal of entire repro system Removal of only germ cells
No effect Animals live up to 60% longer
55
Somatic gonad ____________ but these effects are __________ by the ______________
Extends Counteracts Germline

BMS247 Stem Cells (14 decks)

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