Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1.
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.
Csiszar
Anna
A
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Labinskyy
Nazar
N
Jimenez
Rosario
R
Pinto
John T
JT
Ballabh
Praveen
P
Losonczy
Gyorgy
G
Pearson
Kevin J
KJ
de Cabo
Rafael
R
Ungvari
Zoltan
Z
D000375:Aging; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D031204:Caloric Restriction; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology; D007249:Inflammation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016328:NF-kappa B; D013267:Stilbenes; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins; D000077185:Resveratrol