The effect of an advanced glycation end-product crosslink breaker and exercise training on vascular function in older individuals: A randomized factorial design trial

Madelijn H. Oudegeest-Sander, Marcel G M Olde Rikkert, Paul Smits, Dick H J Thijssen, Arie P J van Dijk, Benjamin D. Levine, Maria T E Hopman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1509-1517
Number of pages9
JournalExperimental Gerontology
Volume48
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Advanced glycation end-products
  • Aging
  • Alagebrium
  • Arterial stiffness
  • Endothelial function
  • Exercise training

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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