Notes- March 13

"Stress Response and Aging" article notes

- Mild stress increases life (calorie restriction, thermal stress, hyperbaric oxygen)
- Transcriptional regulators that respond to stress also influence life span

1. HSF is a transcriptional activator
—> HSF pools monomers

  • HSF-1 activated under stress, the monomers form trimers.
  • translocates to nucleus, binds to heat-shock protein promoters on DNA, the heat shock proteins are chaperones that assist in folding, and help resolve the damage

2. SIRT1: transcriptional activator
—> cell survival, inflammation
transcriptional factor of HSF
*homolog v. ortholog
homolog= same gene from common ancestor
ortholog= similar gene, similar function: not sure if from common ancestor

3. HSF-1 acetylated by acetyltransferase - turns it "off"
so it's dissociated from target genes - keep it from binding to promoter sequences of HSf

SiRNA for SIRT1 inserted a gene into expt. cells that transcribes to mRNA complementary to SIRT1 mRNA

4. HSF-1 acetylates @ ~9 lysine residues (R group of the amino acid compound)
(lysine is an aa in the protein)
Lys80 controls (the lysine found at the 80th position on the aa chain)

paragraph 6

  • Different transcriptional factors control expression of SIRT1 enzyme
  • After transcription SIRT1 is stabilized by the protein, HuR
  • SIRT1 is also controlled by different functional proteins including resveratrol

- Resveratrol found in the skin of red grapes and is a ingredient of red wine (extends life span)

  • The transcriptional factors and protein regulators of SIRT1 are likely to regulate the acetylation of HSF 1
  • Affects DNA binding activity of HSF1

Paragraph 7

  • HSF 1 has effect on SIRT1
  • Calorie restriction increases NAD+/NADH ration b/c of less energy
  • HSF 1 DNA binding and heat shock response is partially reversed by calorie rest., which my be explained by induced expression of SIRT1

Last paragraph
Increase in concentration of SIRT1 causes an increase in HSF1 activity
• Because HSF1 has to be deacetylated before it can bind to DNA
• This can lead to an increase in heat shock factor proteins
o Can increase life expectancy.

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