Telomeres in aging Universal STELA

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Telomeres in agingUniversal STELA a method to
measure telomeres
Why do we age so differently?

• Laila Bendix, MD

Funded by
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Telomeres - structure
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Telomeres - function

• Differentiating from DSB

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Telomeres relate to human aging
Halaschek-Wiener et al 2008
Kimura et al 2008
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Do telomeres also shorten abruptly
12 kb
8 kb
4 kb
1.6 kb
Signal free ends
0.6 kb
Very short telomeres
Graakjaer et al, Aging Cell 2004
0.1 kb
Baird et al, Nat Genet 2003
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Abrupt shortening - mechanisms
Ferenac et al, 2005 J Gerontol A Biol Sci Med
Sci
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Overskrift
Methods for measuring telomeres Mean telomere length Single telomere (chromosome specific) Short telomeres High through-put Material/ template
TRF - () () DNA (large amounts, good quality)
Q-PCR - - DNA (small amounts, good quality)
Flow-FISH - - () Live cells
Q-FISH (metaphase) () - Cells live, dividing
Q-FISH (tissue) - - - Tissue
STELA () (limited to few chromosomes) - DNA (small amounts, good quality)

• Tekst
• Punkt 1
• Punkt 2
• Underpunkt 1

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Universal STELA assay principles
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Telomeres Project part I

• Short telomeres in organismal aging
• Does the number of short telomeres predict
  mortality even better?
• Number of short telomeres and DNA repair
• DNA repair functional studies
• Mitochondrial function
• Snps

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Telomeres and social class

• What do we think
• telomere length is an age-related parameter that
  remains aberrant after many years, and therefore
  is a suitable marker for social stress during
  life.
• What do we know
• Individuals of lower socio-economic status have
  shorter telomeres than their peers of a higher
  socio-economic status. Cherkas et al, 2006
• No association between socio-economic status and
  telomere length. Adams et al, 2007
• What do we have
• CAMB, MONICA and DARC
• Newer and better (?) methods

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Telomeres Project part II

• Establish a high throughput method to measure
  telomeres
• Measure telomere lengths on samples collected in
  the CAMB study
• and later
• Examine other aging related molecular biomarkers
  on same samples
• Short telomeres and social class