PMID- 19549533 OWN - NLM STAT- MEDLINE DCOM- 20090928 LR - 20211020 IS - 1872-6216 (Electronic) IS - 0047-6374 (Print) IS - 0047-6374 (Linking) VI - 130 IP - 8 DP - 2009 Aug TI - Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. PG - 518-27 LID - 10.1016/j.mad.2009.06.004 [doi] AB - 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-kappaB activity. Lifelong CR significantly improved endothelial function, attenuated vascular ROS production, inhibited NF-kappaB 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 TNFalpha elicited oxidative stress, NF-kappaB activation and inflammatory gene expression. By contrast, treatment of CAECs with CR serum attenuated TNFalpha-induced ROS generation and prevented NF-kappaB 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. FAU - Csiszar, Anna AU - Csiszar A AD - Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. FAU - Labinskyy, Nazar AU - Labinskyy N FAU - Jimenez, Rosario AU - Jimenez R FAU - Pinto, John T AU - Pinto JT FAU - Ballabh, Praveen AU - Ballabh P FAU - Losonczy, Gyorgy AU - Losonczy G FAU - Pearson, Kevin J AU - Pearson KJ FAU - de Cabo, Rafael AU - de Cabo R FAU - Ungvari, Zoltan AU - Ungvari Z LA - eng GR - R01 HL077256-02/HL/NHLBI NIH HHS/United States GR - R01 CA111842/CA/NCI NIH HHS/United States GR - R01 HL077256-03/HL/NHLBI NIH HHS/United States GR - HL077256/HL/NHLBI NIH HHS/United States GR - R01 HL077256-01A2/HL/NHLBI NIH HHS/United States GR - HL43023/HL/NHLBI NIH HHS/United States GR - R01 HL077256-04/HL/NHLBI NIH HHS/United States GR - R01 HL077256/HL/NHLBI NIH HHS/United States GR - CA111842/CA/NCI NIH HHS/United States GR - P01 HL043023/HL/NHLBI NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20090621 PL - Ireland TA - Mech Ageing Dev JT - Mechanisms of ageing and development JID - 0347227 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (NF-kappa B) RN - 0 (Stilbenes) RN - EC 3.5.1.- (Sirt1 protein, rat) RN - EC 3.5.1.- (Sirtuin 1) RN - EC 3.5.1.- (Sirtuins) RN - Q369O8926L (Resveratrol) SB - IM MH - *Aging MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Antioxidants/*metabolism/pharmacology MH - *Caloric Restriction MH - Coronary Vessels/cytology MH - Endothelial Cells/cytology MH - Inflammation MH - Male MH - NF-kappa B/metabolism MH - Oxidative Stress MH - Rats MH - Rats, Inbred F344 MH - Resveratrol MH - Sirtuin 1 MH - Sirtuins/*physiology MH - Stilbenes/pharmacology PMC - PMC2756526 MID - NIHMS138013 EDAT- 2009/06/25 09:00 MHDA- 2009/09/29 06:00 PMCR- 2010/08/01 CRDT- 2009/06/25 09:00 PHST- 2009/02/03 00:00 [received] PHST- 2009/05/06 00:00 [revised] PHST- 2009/06/15 00:00 [accepted] PHST- 2009/06/25 09:00 [entrez] PHST- 2009/06/25 09:00 [pubmed] PHST- 2009/09/29 06:00 [medline] PHST- 2010/08/01 00:00 [pmc-release] AID - S0047-6374(09)00085-2 [pii] AID - 10.1016/j.mad.2009.06.004 [doi] PST - ppublish SO - Mech Ageing Dev. 2009 Aug;130(8):518-27. doi: 10.1016/j.mad.2009.06.004. Epub 2009 Jun 21.