Plan for the coming years VELUX FONDEN - 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 Why do we age so differently?

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Plan for the coming years VELUX FONDEN - 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 - Why do we age so differently?

Danish Aging Research Center

Greenhouse Project Line Kirkeby Petersen, MD: Cholesterol and Aging  Observational studies:  Low cholesterol good among younger elderly but associated with higher mortality among the Oldest-Old  Clinical practice:  Cholesterol lowering drugs 

 274 twin pairs age  Blood samples 1997  Follow-up to 2009  Deaths: 289 twins 244 pairs with at least one dead twin  Intrapair comparison: Control for age, sex, genetic factors Cholesterol and Mortality

2,262 (63%) 1,086 (78%) 437 (77%) 166 (74%) 862 died522 died213 died 314 Drop-outs 127 Drop-outs 58 Drop-outs Cohort - Denmark

♂ ♀ ♂ + ♀ : :30 1:10 1:15 92 years – half way to 100

Cross-sectional twin data show association Independent replication in 1905 cohort PARAOXONASE 1 (PON) analysis time genotype = QQgenotype = QR genotype = RR

Does exceptional longevity lead to exceptional levels of disability? Does exceptional longevity lead to exceptional levels of disability? The Fourth Age

Independence in the 1905-Cohort Christensen et al. PNAS, 2008

Independence in the 1905-Cohort Christensen et al. PNAS, 2008

The Failure of Success?