1. 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 -

2. 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

3. 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 oxidative DNA lesions per day

4. DNA damage and repair
O2.-
O2.-

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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
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