DNA damage in aging

15 important questions on DNA damage in aging

What happens with life expactancy and time?

Life expactancy increases one weekend every week

What are environmental causes of dna damage?

uv, radiation, chemicals

What are endogenous causes of dna damage?

ROS
Alkylation
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How many dna lesions are there everyday?

10^4 or 10^5

What is NER and how does it work?

Nucleotide excision repair, XPE and XPC scan the strand if they encounter damage, xpd and xpb break up the strand tfiih comes into play and xpf and xpg cut out the damages strand. XPA recognizes the damage. Strand is cut out and replaced via dna polymerase

What is transcription coupled NER?

Dna polymerase 2 scans dna and stops at damage, than same process repairs the damage

What are the three inherited diseases, which prevent NER from working?

Xeroderma pigmentosum
Cockayne syndrome
Trichothiodystrophy

What is xeroderma pigmentosum?

Severe sun sensitivity, when exposed to sun 2000X higher chance of skin cancer. XPA and XPG are defective

What is cockayne syndrome?

Autosomal recessive disease, growth failure and uv sensitivity, die early. However no skin cancer

What is a main hallmark of aging?

Genomic instability, because it also affects most other hallmarks

What happened in the Ercc delta mice?

Increased cell death and neuronal loss
Decline spatial learning
Progressive motor abnormalities
Reduced LTP

So basically all symptoms of alzheimers

How many significantly changes genes were identified in the cortex?

1119

What are braak stages?

Severity of AD

Why was dietary restriction so useful in ercc1 delta mice?

Because they already had a shortened lifespan the effects could be seen fast

What was the effect seen in mice of dietary restrictions?

Showed overall healthspan improvement, primarily in the nervous system(50% more neurons preserved) because it lowered the amound of endogenously produced DNA damages

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