Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: Role of circulating factors and SIRT1

Anna Csiszar, Nazar Labinskyy, Rosario Jimenez, John T. Pinto, Praveen Ballabh, Gyorgy Losonczy, Kevin J. Pearson, Rafael de Cabo, Zoltan Ungvari

Research output: Contribution to journalArticle

164 Scopus citations

Abstract

Endothelial dysfunction, oxidative stress and inflammation are associated with vascular aging and promote the development of cardiovascular disease. Caloric restriction (CR) mitigates conditions associated with aging, but its effects on vascular dysfunction during aging remain poorly defined. To determine whether CR exerts vasoprotective effects in aging, aortas of ad libitum (AL) fed young and aged and CR-aged F344 rats were compared. Aging in AL-rats was associated with impaired acetylcholine-induced relaxation, vascular oxidative stress and increased NF-κB activity. Lifelong CR significantly improved endothelial function, attenuated vascular ROS production, inhibited NF-κB activity and down-regulated inflammatory genes. To elucidate the role of circulating factors in mediation of the vasoprotective effects of CR, we determined whether sera obtained from CR animals can confer anti-oxidant and anti-inflammatory effects in cultured coronary arterial endothelial cells (CAECs), mimicking the effects of CR. In CAECs cultured in the presence of AL serum TNFα elicited oxidative stress, NF-κB activation and inflammatory gene expression. By contrast, treatment of CAECs with CR serum attenuated TNFα-induced ROS generation and prevented NF-κB activation and induction of inflammatory genes. siRNA knockdown of SIRT1 mitigated the anti-oxidant and anti-inflammatory effects of CR serum. CR exerts anti-oxidant and anti-inflammatory vascular effects, which are likely mediated by circulating factors, in part, via a SIRT1-dependent pathway.

Original languageEnglish (US)
Pages (from-to)518-527
Number of pages10
JournalMechanisms of Ageing and Development
Volume130
Issue number8
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

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Keywords

  • Aging
  • Calorie restriction
  • Inflammation
  • Oxidative stress
  • Resveratrol

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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