Download Telomeres in aging Universal STELA

Why do we age so differently?
Telomeres in aging
Universal STELA – a method to measure telomeres
Laila Bendix, MD
Funded by:
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
VELUX FONDEN
Telomeres - structure
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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Telomeres - function
 Differentiating from DSB
 Shorten with cell aging
 End replication problem
Harley et al 1990, Nature
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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Telomeres relate to human aging
Halaschek-Wiener et al 2008
Kimura et al 2008
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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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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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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Abrupt shortening - mechanisms
Passos et al 2007, NAR
Ferenac et al, 2005; J Gerontol A Biol Sci Med Sci
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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Methods for
measuring
telomeres
Mean
telomere
length
Single
telomere
TRF
+
-
Short
telomeres
High
throughput
Material/
template
(+)
(+)
DNA
-
++
DNA
-
(+)
Live cells
Overskrift
(chromosome
specific)
 Tekst
Q-PCR  Punkt
+1
 Punkt 2
1
Flow-FISH Underpunkt
+
-
(large amounts, good
quality)
(small amounts, good
quality)
Q-FISH
(metaphase)
+
++
(+)
-
Cells: live,
dividing
Q-FISH
(tissue)
+
-
-
-
Tissue
STELA
(+)
-
++
++
to few
D A N I S H(limited
A
GING RESEARCH CENTER
chromosomes)
www.sdu.dk/darc
DNA
-
(small amounts, good
quality)
Universal STELA – assay principles
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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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
 Snp´s
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
-
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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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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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
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DANISH AGING RESEARCH CENTER
www.sdu.dk/darc
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