1st year evaluation meeting1st year evaluation meeting

18 – 19 May 2009Hotel Marienlyst, Helsingor

DDanishanish A Agingging R Researchesearch C Centerenter

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?

Focus of molecular biology of aging Focus of molecular biology of aging researchresearch

- University of Aarhus- University of Aarhus

Genomic instability DNA damage and DNA repair Role of mitochondria Role of genes deficient in premature aging

syndromes

Smoking

Metabolism

Mitochondria

UV- lightRadioactivity

Different sources of DNA damaging Different sources of DNA damaging agentsagents

Air pollution

A single mammalian cell sustains up to 10.000 oxidative DNA lesions per day

O2.-

O2.-

O2.-

O2.-

O2.-

O2.-

O2.-

DNA damage and repairDNA damage and repair

MitochondriMitochondriaa

2H+

H+

H+H+

H+

H+

NADH

NAD+H+

H+

H+

H+

H+H+

H+

ADP+ P

ATP

Complex II

Complex III

Complex I V

ATP Synthethase

O2 +H2O

e-

e-

ROS

O2

O2 2O2*-

+2H+H2O2

SOD2H2O

Gpx

2GSH GSSG

OH2- OH-

mtDNA BER

Complex I

Outer membrane

Inner membrane

Matrix

Mitochondrial free radical theory of agingMitochondrial free radical theory of aging(Harman, 1973)(Harman, 1973)

ROS Mitochondrial oxidative stress

Oxidative damage Proteins

Nucleic AcidsLipids

Carbohydrates

Repair mechanimsDNA repair

Protein Degradation

Accumulation of Lesions -DNA mutations

-Protein aggregation

AntioxidantsmnSOD

Gluthathione system

Aging

Disease

Dysfunctional

mitochondria

Frailty ?

Cells from patients suffering from premature aging syndromes- and purified gene products

Blood samples from twins and individuals from other relevant other cohorts

Tissues and cellular extracts from laboratory mice

First DARC year progressFirst DARC year progress- University of Aarhus- 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

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

Desimination, meetings and summer schools

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.

Appearance in mediaAppearance in media

Teaching courses and supervision of students 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