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measuring ageing Flashcards

1
Q

whats Gompertz’ law?

A

mortality increases with age, every 8 years mortality risk doubles

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2
Q

what has the most power over ageing ?

A

genetics - mice live longer than humans

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3
Q

what does Harvath clock relate to ?

A

rate of ageing and methylation

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4
Q

whats extrinsic mortality ?

A

risk of dying of something other than ageing

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5
Q

why isnt ageing selected for?

A

only matter to get the individual to survive to reproduce thats why humans begin to age after 40

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6
Q

whats the antagonist pleiotropy mutation theory ?

A

mutations arise and those which turn out to have negative effects in the long term but positive in the short term are selected for cause the individual lives long enough to reproduce

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7
Q

what are the issues with increasing age?

A

methods which induce increase in age may cause other health issues - reduced fitness/fertility

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8
Q

what is the disposal soma theory ?

A

germline is immoral but soma cells arent . animals divide up energy between progeny production or long term survival - life history

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9
Q

how can measure yeast reproduciton ?

A

mother cell has a scar from when the daughter cell has divided.

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10
Q

how does an old mother yeast cell not produce an old daughter cell?

A

has an age barrier between the two cells when they are connected - stops ageing macromolecules from passing over

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11
Q

what are examples of the ageing macromolecules?

A

senescence factors, extra chromosomal ribosomal dna circles and damaged proteins

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12
Q

how does forward/ classical genetics work ?

A

mutagenise germ-line then scan offspring for muts ( F2 for recessive muts) then map for the genes changed

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13
Q

how does reverse genetics work?

A

find a gene of interest then mut it, characterise phenotype produced to work out function of gene

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14
Q

what does EMS do ?

A

chemcial mutagenesis - random muts induced

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15
Q

what life stage do c. elegans go into if there is a lack of food in L1 ?

A

diapause daucer phase

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16
Q

what is DAF 2?

A

insulin like receptor

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17
Q

what is DAF16?

A

foxotranscription factor

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18
Q

when can DAF16 enter the nucleus ?

A

when it isnt pp and this cause the animal to live longer

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19
Q

when are mutations normally visible ?

A

F2 - homozygous and recessive

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20
Q

how do you work out which gene has mutated?

A

map to see how its inherited, cross it to see if it is similar with other mutants, - genetic linkage see how similar to see where on the chromosome it is

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21
Q

what are the two daucer mutants ?

A

DAFC adn DAFD

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22
Q

what does DAFC do ?

A

forms dauer - DAF2 +23

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23
Q

what does DAFD do ?

A

doesnt form dauer daf 16+18

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24
Q

what is epistasis analysis ?

A

work out if one gene is dependant on another

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25
example of epistasis ?
daf 16 hides the effect of daf 2 therefore daf2 is upstream of daf 16 gene
26
what is non complementation ?
when you cross two genes and they produce a homologous phenotype
27
how do you narrow down where a gene is on a chromosome ?
use deletion mutants
28
what is Daf2 a homolog to ?
human igf/insulin receptor
29
what happens when insulin binds to the igf/insulin receptor ?
causes autophosporylation on tyrosine receptors
30
what do pp tyrosine attract?
AAP1 adaptor
31
what does the AAP1 adaptor carry with it ?
AGE1P13 KINASE
32
What does AGE1 P13 kinase do once it is at the plasma membrane ?
pp P1(4,5)P2 -> P1 (3,4,5)P3
33
what does P1(3,4,5)p3 do?
acitvates other kinase which tirggers serine 3k to pp other proteins
34
what happens when daf16 is pp ?
prevents it from entering the nucleus
35
what is daf16?
FOXO transcription factor
36
effects of this drosphila and mice models ?
that the mutants are smaller and have fertility
37
how do mutants compare to wt ?
daf2 cannot survive in models as they have a lower reproduction rate but age1 can just not under starvation conditions
38
which mutant is healthier?
age1 is healthier than daf2
39
how does RNA interference work ?
knocks down gene expression, feed worms ecoli that produce dsDNA for the worm gene , the ds DNA is then taken up by the intestinal cells
40
how could timed intervention work to reduce the negative side effects seen in ageing mutants ?
timed intervention, induce the ageing genetic changes at the point where progeny production is not effected
41
how does time compression work ?
when do decrease the temp of the worms they tend to live longer and this graph is very similar to the one seen when damage rate is decreased
42
what is the theory of interdependent network of ageing?
network model that resembles ageing , through nodes rate of decay, rate of repair ...
43
what is dietary restriction ?
reduced food intake without malnutrition
44
how does dietary restriction impact ageing ?
increases lifespan
45
how can you judge if specimens are experiencing malnutrition?
see if they grow properly
46
how can you see if theres something in the food that is causing ageing?
give more food - see if risk of death increases or if health increase
47
what do DR tents show?
as food intake increases so does progeny production, but lifespan decreases
48
example of an artefact ?
osmotic stress
49
how does low protein impact lifespan?
increases it
50
what do animals regulate when eating?
protein not calories
51
what do sirtuins do ?
sense metabolism sir(1-6)
52
what does a decrease in glucose imapct yeast lifespan?
increases it
53
what does over expression of sir2 do ?
increases replication lifespan and decrease DNA circles- senescence factors
54
what does NAD do?
key in metabolism, decreases as we age
55
what activates NAD?
resveratrol
56
what does sIR2 do?
cause mitochondrial unfolding response which increases lifespan
57
what does TOR stand for?
Target of rapamycin
58
what does tor effect?
transcription, translation and autophagy modifications
59
how does a decrease in tor activation impact lifespan?
increases it
60
what disease is metformin used to treat?
diabetes
61
why might microbes effect ageing?
because there is no selection pressure against microbes that impact ageing after reproduction
62
what does the shikimic acid pathway do?
allows plants and animals to make aromatic ring comounds
63
what does the PABA pathway do?
enables folate production
64
what blocks the PABA pathway ?
SMX- sulphonamide drugs
65
why is folate important?
needed for enzymatic cycles - biosynthesis of compounds
66
what happen folate levels decrease?
cycle still continues just at a slower rate, growth still occurs - same progeny
67
why might a decrease in folate in ecoli causing the c elegans ot live longer?
less likely to engage in invasive pathogenesis and toxin production
68
why might a decrease in folate in c elegans cause them to live longer?
folate restriction might be similar to dietary restriction other effect on host metabolism ??
69
what protein allows the up take of animal folate ?
Gcp-2.1
70
how does Gcp-2.1 work ?
removes polyglutamate chains on folates allowing them to be absorbed easier
71
where is folic acid found ?
in the lab not nature
72
where is folinic acid found ?
in nature
73
why might folinic acid be taken up by c elegans easier?
because its found in nature , worms have a pathway for uptake
74
what does kanamycin do?
increase worm lifespan and decreases ecoli growth
75
what is PABA-glu ?
the random breakdown of folic acid which ecoli can utilise

Ageing (3 decks)

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