Danish Aging Research Center

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Presentation transcript:

Danish Aging Research Center Why do we age so differently? 1st year evaluation meeting 18 – 19 May 2009 Hotel Marienlyst, Helsingor Danish Aging Research Center 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

Focus of molecular biology of aging research - University of Aarhus Genomic instability DNA damage and DNA repair Role of mitochondria Role of genes deficient in premature aging syndromes

Different sources of DNA damaging agents Radioactivity UV- light Air pollution Smoking Metabolism O2.- O2.- O2.- O2.- O2.- Mitochondria A single mammalian cell sustains up to 10.000 oxidative DNA lesions per day

DNA damage and repair O2.- O2.-

Mitochondria ROS 2O2*- H2O2 OH2- OH- Outer membrane Inner membrane NADH NAD+ ADP+ P ATP Complex II Complex III Complex I V ATP Synthethase O2 + H2O e- ROS 2O2*- +2H+ H2O2 SOD 2H2O Gpx 2GSH GSSG OH2- OH- mtDNA BER Complex I Outer membrane Inner membrane Matrix

Mitochondrial free radical theory of aging (Harman, 1973) Oxidative damage Proteins Nucleic Acids Lipids Carbohydrates ROS Mitochondrial oxidative stress Repair mechanims DNA repair Protein Degradation Antioxidants mnSOD Gluthathione system Accumulation of Lesions -DNA mutations -Protein aggregation Frailty ? Dysfunctional mitochondria Aging Disease

Blood samples from twins and individuals from other relevant other cohorts Cells from patients suffering from premature aging syndromes - and purified gene products Tissues and cellular extracts from laboratory mice

First DARC year progress - University of Aarhus Ph.D. students Enrollment (maternity leave and substitute) Course activities Project start up – establishment of techniques Project progress Established assay for detection of strand break repair in single cells (comet assay) Established immunofluoresence technique for detection of cellular damage recognition Established fluorometric techniques for measurement of mitochondrial function (membrane potential) Established immuno detection assay for measurement of protein oxidation (carbonylation) in nuclear and mitochondrial DNA Initiated measurement of DNA repair capacity in twin samples Selected samples for study on frailty and mitochondrial function

Desimination, meetings and summer schools Workshop on Aging – from Molecules to Population”, Elsinore, May 2008 Minisymposium on “DNA Strand Break Repair in Aging”, Aarhus, Jan. 2009 3rd US-EU BER conference on “Repair of endogenous damage”, Galveston, Texas, Febr. 2009 MiMage conference on “Mitochondria in Aging and Age-related Disease”, Les Diablerets, Switzerland, Sept. 2009 Summer school on “Mitochondria in Health and Disease”, Roskilde, June 2009

Teaching courses and supervision of students Appearance in media DR1 Radio: Det optimerede menneske. Fall 2008 DR1 Radio: Videnskabens verden. Fall 2008. DR2 TV: Stress gør ung og livet langt, Viden Om - January 20 2009. Teaching courses and supervision of students University course on Genome Instability and Aging ”Folke-university” course on Molecular Biology of Aging Supervision of bachelor, master and ph.d.-students