Ageing And Age Related Diseass

Question 1

What is ageing

Answer 1

Progression loss of function accompanied with increased mortality and reduced fertility

Question 2

Ageing isn’t programmed. What does this mean

Answer 2

No gene directly causes ageing and death. It is through natural processes

Question 3

What natural processes cause ageing

Answer 3

Accumulation of damage eg to dna, proteins and lipids (peroxidation of lipids)

From mt ros released in metabolism

Question 4

What repair systems exist

Answer 4

Antioxidants and dna repair mechanisms eg parp

Question 5

Why would you study ageing

Answer 5

Major risk factor of age related disease like cvd, cancers, Alzheimer’/neurodegenerative disease

Question 6

What is medawars ageing theory

Answer 6

There is a selective shadow which is a period of time after reproduction etc that natural selection has no effect on survival of the person.

We naturally build up late onset deleterious mutations in this selective shadow

Question 7

Give an example of a late onset gene mutation (the only example of medawars)

Answer 7

Huntingtons disease around 50

Question 8

What does antagonistic pleiotropy theory mean by Williams

Answer 8

Genes deemed beneficial in early life like oestrogen is detrimental in later life eg ovarian cancer risk

Question 9

What is the disposable soma theory of ageing

Answer 9

Organisms allocate their resources/energy depending on their needs. Eg mice have short life spans so they don’t allocate energy to maintenance and repair systems they use it for reproduction.

We have enough resources to last a longer life span ie use it for maintenance and repair

Question 10

What causes the ageing according to disposable soma theory

Answer 10

The trade off for reproduction will then reduce maintenance and repair energy = ageing

Vice versa

Question 11

What is the big enzyme for dna repair which is seen more active in human cells vs rat cells ie why we have long life span

Answer 11

Parp1

Question 12

What does plasticity of ageing mean

Answer 12

Ability to change the rate of ageing

Question 13

Explain how mutations in the insulin pathway have been found to be anti ageing in model organisms

Answer 13

Daf 2 is gene for igf receptor in c elegans
If single gene mutations occur this increased life span as it allowed daf-16 which is an orthologue to foxo tf to then ttanslocate to nucleus and allow txn of genes like antioxidants = reduced ageing process

Question 14

What sort of gene antioxidant does dsf16 cause txn of

Answer 14

Superoxide dismutase

Question 15

What other animals has this been proved I.e stopping nutrient sensing via a insulin like system = increase lifespans

Answer 15

Mice, drosophila and c elegans

Question 16

What is the reasons for human plasticity in lifespan from 1800s

Answer 16

Better healthcare and declined child mortality (NOT GENES)

Question 17

Which other nutrient sensing pathway is involved this time in increasing lifespan of drosophila

Answer 17

Tor pathway

Question 18

What inhibits tor pathway which is usually activated by nutrients

Answer 18

Tsc1 and 2

Question 19

What does tor promote and therefore reduces something important to stop ageing

Answer 19

Promotes cell growth and reduces autophagy

Question 20

Why is autophagy important for reduced ageing rates

Answer 20

Clears damaged mitochondria stopping dysfunction also allows normal dna repair (see fr)

Question 21

Which age related diseases need autophagy to help reduce their production

Answer 21

Clears ab deposits in Alzheimer’s

Clears the mutant Htt gene

Question 22

Give 2 ways calorie restriction can be seen beneficial in plasticity of ageing

Answer 22

Blocks tor pathway = autophagy occurs and reduced cell proliferation/growth

Blocks the insulin like pathway = foxo activation

Question 23

Which genes have been found as candidate genes early on for genetic contributions to ageing

Answer 23

Apoe (encodes a lipoprotein which transports lipids)

Foxo3a - tf for oxidative stress and apoptosis

Question 24

In a meta-analysis of gwas studying link between genes of ageing and age related diseases, which gene was only one found significantly enriched in 3/5 of the age related disease categories

Answer 24

Apoe

Question 25

Which Apoe isoform been linked in other studies as a risk allele for ageing and some age related diseases

Answer 25

Apoe e4

Question 26

How was Apoe e4 seen to affect Alzheimer’s and a major risk factor with an or of 14.9

Answer 26

Causes ab deposition, aggregation and neuronal toxicity

Question 27

How is the same allele linked to coronary heart disease

Answer 27

Causes hyperlipidemia and hypercholestrolemia

Question 28

Which types of genetic diseases were the first to show ageing can be affected by genes/gene mutations

Answer 28

Progeria diseases where they age early eg Werner’s syndrome

Question 29

What sort of drugs to try slow ageing are being made

Answer 29

Against mtor pathway

Question 30

Is there epigentic changes during ageing whcih may account for ageing progression?

Answer 30

Yes, for example in epigentic lecture there are links to reduced heterochromatin and ageing

Also age related neurodegeneration