1. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Telomeres in aging Universal STELA – a method to measure telomeres Why do we age so differently? Laila Bendix, MD VELUX FONDEN Funded by:

2. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Telomeres - structure

3. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Telomeres - function  Differentiating from DSB  Shorten with cell aging Harley et al 1990, Nature  End replication problem

4. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Telomeres relate to human aging Kimura et al 2008 Halaschek-Wiener et al 2008

5. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Do telomeres also shorten abruptly Do telomeres also shorten abruptly Signal free ends Graakjaer et al, Aging Cell 2004 12 kb 8 kb 4 kb 1.6 kb 0.6 kb 0.1 kb Very short telomeres Baird et al, Nat Genet 2003

6. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Abrupt shortening - mechanisms Passos et al 2007, NAR Ferenac et al, 2005; J Gerontol A Biol Sci Med Sci

7. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Overskrift  Tekst  Punkt 1  Punkt 2  Underpunkt 1

8. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc Universal STELA – assay principles Universal STELA – assay principles

9. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc 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

10. - D A N I S H A G I N G R E S E A R C H C E N T E R - 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

11. - D A N I S H A G I N G R E S E A R C H C E N T E R - www.sdu.dk/darc 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