TY - JOUR
T1 - The effect of an advanced glycation end-product crosslink breaker and exercise training on vascular function in older individuals
T2 - A randomized factorial design trial
AU - Oudegeest-Sander, Madelijn H.
AU - Rikkert, Marcel G M Olde
AU - Smits, Paul
AU - Thijssen, Dick H J
AU - van Dijk, Arie P J
AU - Levine, Benjamin D.
AU - Hopman, Maria T E
N1 - Funding Information:
This work was supported by The Netherlands Heart Foundation (grant 2006B235 to Mrs. Oudegeest-Sander and 2009T064 to Dr. Thijssen). The overall study was also supported by National Institutes of Health (grant R01AG017479 to Dr. Levine from the National Institute of Aging ). The authors declare that no competing interests are associated with this study.
PY - 2013/12
Y1 - 2013/12
N2 - Aging leads to accumulation of irreversible advanced glycation end-products (AGEs), contributing to vascular stiffening and endothelial dysfunction. When combined with the AGE-crosslink breaker Alagebrium, exercise training reverses cardiovascular aging in experimental animals. This study is the first to examine the effect of Alagebrium, with and without exercise training, on endothelial function, arterial stiffness and cardiovascular risk in older individuals. Forty-eight non-exercising individuals (mean age 70±4years) without manifest diseases or use of medication were allocated into 4 groups for a 1-year intervention: Exercise training & Alagebrium (200mg/day); exercise training & placebo; no exercise training & Alagebrium (200mg/day); and no exercise training & placebo. We performed a maximal exercise test (VO2max) and measured endothelial function using venous occlusion plethysmography and intra-arterial infusion of acetylcholine, sodium nitroprusside and NG-monomethyl-l-arginine. Arterial stiffness was measured using pulse wave velocity. Cardiovascular risk was calculated using the Lifetime Risk Score (LRS). In the exercise training groups, LRS and VO2max improved significantly (23.9±4.5 to 27.2±4.6mLO2/min/kg, p<0.001). Endothelial response to the vasoactive substances did not change, nor did arterial stiffness in any of the four groups. In conclusion, one year of exercise training significantly improved physical fitness and lifetime risk for cardiovascular disease without affecting endothelial function or arterial stiffness. The use of the AGE-crosslink breaker Alagebrium had no independent effect on vascular function, nor did it potentiate the effect of exercise training. Despite the clinical benefits of exercise training for older individuals, neither exercise training nor Alagebrium (alone or in combination) was able to reverse the vascular effects of decades of sedentary aging.
AB - Aging leads to accumulation of irreversible advanced glycation end-products (AGEs), contributing to vascular stiffening and endothelial dysfunction. When combined with the AGE-crosslink breaker Alagebrium, exercise training reverses cardiovascular aging in experimental animals. This study is the first to examine the effect of Alagebrium, with and without exercise training, on endothelial function, arterial stiffness and cardiovascular risk in older individuals. Forty-eight non-exercising individuals (mean age 70±4years) without manifest diseases or use of medication were allocated into 4 groups for a 1-year intervention: Exercise training & Alagebrium (200mg/day); exercise training & placebo; no exercise training & Alagebrium (200mg/day); and no exercise training & placebo. We performed a maximal exercise test (VO2max) and measured endothelial function using venous occlusion plethysmography and intra-arterial infusion of acetylcholine, sodium nitroprusside and NG-monomethyl-l-arginine. Arterial stiffness was measured using pulse wave velocity. Cardiovascular risk was calculated using the Lifetime Risk Score (LRS). In the exercise training groups, LRS and VO2max improved significantly (23.9±4.5 to 27.2±4.6mLO2/min/kg, p<0.001). Endothelial response to the vasoactive substances did not change, nor did arterial stiffness in any of the four groups. In conclusion, one year of exercise training significantly improved physical fitness and lifetime risk for cardiovascular disease without affecting endothelial function or arterial stiffness. The use of the AGE-crosslink breaker Alagebrium had no independent effect on vascular function, nor did it potentiate the effect of exercise training. Despite the clinical benefits of exercise training for older individuals, neither exercise training nor Alagebrium (alone or in combination) was able to reverse the vascular effects of decades of sedentary aging.
KW - Advanced glycation end-products
KW - Aging
KW - Alagebrium
KW - Arterial stiffness
KW - Endothelial function
KW - Exercise training
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U2 - 10.1016/j.exger.2013.10.009
DO - 10.1016/j.exger.2013.10.009
M3 - Article
C2 - 24400341
AN - SCOPUS:84887549833
SN - 0531-5565
VL - 48
SP - 1509
EP - 1517
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 12
ER -