Ageing And Age Related Diseass Flashcards
What is ageing
Progression loss of function accompanied with increased mortality and reduced fertility
Ageing isn’t programmed. What does this mean
No gene directly causes ageing and death. It is through natural processes
What natural processes cause ageing
Accumulation of damage eg to dna, proteins and lipids (peroxidation of lipids)
From mt ros released in metabolism
What repair systems exist
Antioxidants and dna repair mechanisms eg parp
Why would you study ageing
Major risk factor of age related disease like cvd, cancers, Alzheimer’/neurodegenerative disease
What is medawars ageing theory
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
Give an example of a late onset gene mutation (the only example of medawars)
Huntingtons disease around 50
What does antagonistic pleiotropy theory mean by Williams
Genes deemed beneficial in early life like oestrogen is detrimental in later life eg ovarian cancer risk
What is the disposable soma theory of ageing
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
What causes the ageing according to disposable soma theory
The trade off for reproduction will then reduce maintenance and repair energy = ageing
Vice versa
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
Parp1
What does plasticity of ageing mean
Ability to change the rate of ageing
Explain how mutations in the insulin pathway have been found to be anti ageing in model organisms
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
What sort of gene antioxidant does dsf16 cause txn of
Superoxide dismutase
What other animals has this been proved I.e stopping nutrient sensing via a insulin like system = increase lifespans
Mice, drosophila and c elegans
What is the reasons for human plasticity in lifespan from 1800s
Better healthcare and declined child mortality (NOT GENES)
Which other nutrient sensing pathway is involved this time in increasing lifespan of drosophila
Tor pathway
What inhibits tor pathway which is usually activated by nutrients
Tsc1 and 2
What does tor promote and therefore reduces something important to stop ageing
Promotes cell growth and reduces autophagy
Why is autophagy important for reduced ageing rates
Clears damaged mitochondria stopping dysfunction also allows normal dna repair (see fr)
Which age related diseases need autophagy to help reduce their production
Clears ab deposits in Alzheimer’s
Clears the mutant Htt gene
Give 2 ways calorie restriction can be seen beneficial in plasticity of ageing
Blocks tor pathway = autophagy occurs and reduced cell proliferation/growth
Blocks the insulin like pathway = foxo activation
Which genes have been found as candidate genes early on for genetic contributions to ageing
Apoe (encodes a lipoprotein which transports lipids)
Foxo3a - tf for oxidative stress and apoptosis
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
Apoe
Which Apoe isoform been linked in other studies as a risk allele for ageing and some age related diseases
Apoe e4
How was Apoe e4 seen to affect Alzheimer’s and a major risk factor with an or of 14.9
Causes ab deposition, aggregation and neuronal toxicity
How is the same allele linked to coronary heart disease
Causes hyperlipidemia and hypercholestrolemia
Which types of genetic diseases were the first to show ageing can be affected by genes/gene mutations
Progeria diseases where they age early eg Werner’s syndrome
What sort of drugs to try slow ageing are being made
Against mtor pathway
Is there epigentic changes during ageing whcih may account for ageing progression?
Yes, for example in epigentic lecture there are links to reduced heterochromatin and ageing
Also age related neurodegeneration
