The autophagy enhancer spermidine reverses arterial aging

Mech Ageing Dev. Jul-Aug 2013;134(7-8):314-20. doi: 10.1016/j.mad.2013.04.004. Epub 2013 Apr 20.

Abstract

Arterial aging, characterized by stiffening of large elastic arteries and the development of arterial endothelial dysfunction, increases cardiovascular disease (CVD) risk. We tested the hypothesis that spermidine, a nutrient associated with the anti-aging process autophagy, would improve arterial aging. Aortic pulse wave velocity (aPWV), a measure of arterial stiffness, was ~20% greater in old (O, 28 months) compared with young C57BL6 mice (Y, 4 months, P<0.05). Arterial endothelium-dependent dilation (EDD), a measure of endothelial function, was ~25% lower in O (P<0.05 vs. Y) due to reduced nitric oxide (NO) bioavailability. These impairments were associated with greater arterial oxidative stress (nitrotyrosine), superoxide production, and protein cross-linking (advanced glycation end-products, AGEs) in O (all P<0.05). Spermidine supplementation normalized aPWV, restored NO-mediated EDD and reduced nitrotyrosine, superoxide, AGEs and collagen in O. These effects of spermidine were associated with enhanced arterial expression of autophagy markers, and in vitro experiments demonstrated that vascular protection by spermidine was autophagy-dependent. Our results indicate that spermidine exerts a potent anti-aging influence on arteries by increasing NO bioavailability, reducing oxidative stress, modifying structural factors and enhancing autophagy. Spermidine may be a promising nutraceutical treatment for arterial aging and prevention of age-associated CVD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging* / drug effects
  • Aging* / metabolism
  • Aging* / pathology
  • Animals
  • Arteries* / metabolism
  • Arteries* / pathology
  • Arteries* / physiopathology
  • Autophagy / drug effects*
  • Biomarkers / metabolism
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control
  • Dietary Supplements*
  • Endothelium, Vascular* / metabolism
  • Endothelium, Vascular* / pathology
  • Endothelium, Vascular* / physiopathology
  • Gene Expression Regulation / drug effects
  • Glycation End Products, Advanced / metabolism
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Spermidine / pharmacology*
  • Superoxides / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism
  • Vascular Stiffness / drug effects
  • Vasodilation / drug effects

Substances

  • Biomarkers
  • Glycation End Products, Advanced
  • Superoxides
  • 3-nitrotyrosine
  • Tyrosine
  • Spermidine