stress and the aging heart
DESCRIPTION
Department of Molecular and Cellular Sport Medicine (Head: Prof. Dr. W. Bloch) Institute of Cardiology and Sport Medicine German Sport University Cologne. Stress and the Aging Heart. PD Dr. Klara Brixius. Stress and the Aging Heart. ‚Aging‘. Getting older. Getting old. - PowerPoint PPT PresentationTRANSCRIPT
Stress and the Aging Heart
PD Dr. Klara Brixius
Department of Molecular and Cellular Sport Medicine(Head: Prof. Dr. W. Bloch)
Institute of Cardiology and Sport MedicineGerman Sport University Cologne
‚Aging‘
Getting older Getting oldCellular Growth/Regeneration Degeneration/Senescence
Stress and the Aging Heart
Stress and the Aging Heart
Cardiac Stress
Oxidative Stress
Stress and the Aging Heart
‚Oxidative Stress‘ and Antioxidant Defense Mechanisms
Gender Differences in the Aging Heart,
Prevention and Therapeutic Consequences
Oxidative Stress : Definition
O2
O O
O O
Superoxide Anion
O2
O O
Oxygen Molecule
Oxidative Enzymes : Cytochrome C Oxidase
Oxidative Phosphorylation
Inner SideMatrix
Outer SideIntermembraneous Space
Oxidative Enzymes : NAD(P)H-Oxidases
Oxidative Enzymes : Xanthine-Oxidases
Modified from Tossios and Mehlhorn 2004, Blickpunkt der Mann 2: 36-39
Ph
ysic
al E
xerc
ise
Isc
he
mia
ATP
ADP
Adenosine
HypoxanthineXanthine oxidase
Xanthine + O2
Xanthine oxidase O2
+Urate
ROS and the Aging Heart
Lipid peroxidation(cellular membranes)
Protein oxidation(Cytosol)
DNA oxidation(Nucleus)
Cellular Dysfunction
ROS and the Aging Heart
Cellular Dysfunction
Hyperglycemia
Angiotension, etc.
oxLDL
CardivascularRisk
Factors
Webside Prof. S. HardingImperial College London
ROS and the Aging Heart
modified from Brandes et al. Cardiovasc Res (2005) 66: 286-294
Tissue Degeneration
Hyperglycemia
Angiotension, etc.
oxLDL
CardivascularRisk
Factors
Oxidative Stress : Definition
Antioxidative Defense
ROS
Radical Buffer Systems:•Vitamines•Thioredoxins/Peroxiredoxins•Proteins (Albumin, Thiols)
ROS and Antioxidative Defense Mechanisms
O2
O2 H2O2
OH
H2O
1O2
SOD (Mn, Cu) Katalase
Cytochrome C
Oxidase
NAD(P)H
Oxidase
Xanthin Oxiase
Gluthatione Peroxidase (Se, GSH)
*
0
1
2
3
4
5
n=6 n=6 n=9 n=9
8-Isoprostan
Strassburger et al. Free Radical Biology & Medicine (2005) 38: 1458-1470
No increase in the vessel/myocyte ratio in MnSOD-knockout mice after endurance training
Ves
sel/m
yocy
te
Con
Trai
n
Con
Trai
n
Brixius, Bloch et al. 2006, in preparation
*
*: p<0.05
MnSOD-KNOWild type
Wild type MnSOD-KNO
Adaptation of Antioxidative Defense Mechanisms
modified from Gutteridge 1992, Free Rad Res Comm 19: 598-620
AdaptationAntioxidants
Oxidative Stress
Maladaptation
Differential Down-Regulation of Peroxiredoxin Isoformsin Human Failing Myocardium
Peroxiredoxin 1 Peroxiredoxin 2 Peroxiredoxin 3 Peroxiredoxin 4 Peroxiredoxin 5 Peroxiredoxin 6
NF DCM
01020304050607080
NF DCM0306090
120150180210240
DU/µg prot. DU/µg prot.
NFn=6
DCM
NF DCM
0
20
40
60
80
100
120
DU/µg prot.
NF DCM
p=0.08
0
5
10
15
20
25
30
35DU/µg prot. p=0.06
NF DCM NF DCM
0
10
20
30
40
50
p=0.07DU/µg prot.
NF DCM
NF DCM
NF DCM0
4
8
12
16
20
DU/µg prot. p=0.06
NF DCM
NF DCM
Number of experiments,NF and DCM: n=6 each
Brixius, Bloch, 2006, in preparation
Stress and the Aging Heart
‚Oxidative Stress‘ and Antioxidant Defense Mechanisms
Gender Differences in the Aging Heart
Therapeutic Consequences ?
Stress and the Aging Heart: Gender
Vina et al. 2005, FEBS Letters 579: 2541-2545
Antioxidative Mechanisms of Estrogenes
No
n g
eno
mic
Rap
idG
eno
mic
Slo
w
Estrogen
Antioxidative Enzymes
ER
Estrogen
ERE
ER
Oxidative Defense
De Simone et al., Hypertension 31: 1077-1082, 1998
Gender-Specific Differences in Cardiac Function
Men (n = 229)
Women (n = 164)
Age, y 46 ± 12 44 ± 13
Body weight, kg 74 ± 8 61 ± 9§
Body height, m 1.75 ± 0.08 1.62 ± 0.07 §
Heart rate, bpm 66 ± 11 69 ± 11
Blood pressure, mm Hg 121/75 ± 9/7 114/70 ± 12/8 +
LV mass, g 155 ± 33 111 ± 25§
Stroke volume, ml/beat 78 ± 16 64 ± 12§
Stroke work, g-m/beat 136.15 ± 30.38 105.21 ± 25.06§
*P<05; +P<005; §P<0001 for gender difference within age stratum.
Stroke Work/LV Mass,g-m/beat per gram
Stroke Work Index/LVMass, g-m/beat/m2
per gram
0.89 ± 0.17 0.47 ± 0.1
*
Men (n = 229)
Women (n = 164) 0.97 ± 0.23 0.59 ± 0.15 *
De Simone et al., Hypertension 31: 1077-1082, 1998
Ratio of Stroke Work to LV Mass in Normotensive, Normal-Weight Individuals
LV indicates left ventricular* P < 0001 vs men.
Gender-Specific Differences in Cardiac Function
Gender Differences in Mitochondrial Function
Male
Female
6000
4000
2000
0
pm
ol O
2 *
s-1 *
g t
issu
e-1
*
Justo et al., Am J Physiol 289: C372-378, 2005
Male Female
Vina et al. 2005, FEBS Letters 579: 2541-2545
Gender Differences in Oxidative Defense Mechanisms
Gender Differences in ROS Generation at Physical Exercise
Esbjörnsson-Liljedahl et al. J Appl Physiol 93: 1075-1083, 2002
30 s cycle sprint 20 min rest
Estrogen
modified from Brandes et al. Cardiovasc Res (2005) 66: 286-294
+
Akt
, N
O
Cherif et al. (2003) Nucleic Acids Research 31: 1576-1583
Gender Differences in Telomere Lengthening
Gender Differences in Oxidative Stress and Cardiac Aging - Prevention and Therapeutical Consequences:
Conclusions and Perspectives
Hormonal Replacement Therapy
Nutritional Supplementation (e.g. phytoestrogenes?, gender-specific nutrion recommendations...)
Oxidative Stress and Physical Exercise‚Cologne Marathon‘
0
100
200
300
400
500
600
700
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
beforeafter
Reactive Oxygen Metabolites
Laatsch, Türk, Predel Brixius, Bloch et al. 2006 unpublished results + Antioxidants
Arb
itra
ry U
nit
s
Gender Differences in Oxidative Stress and Cardiac Aging - Prevention and Therapeutical Consequences:
Conclusions and Perspectives
Hormonal Replacement Therapy
Nutritional Supplementation (e.g. phytoestrogenes?, gender-specific nutrion recommendations...)
Physical exercise in young and old persons
The Cologne Cardiac Anti-Aging Program
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