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.
|Number of pages
|Mechanisms of Ageing and Development
|Published - Aug 2009
Bibliographical noteFunding Information:
This work was supported by grants from the American Diabetes Association (to ZU), the American Federation for Aging Research (to AC), the NIH (HL077256 and HL43023, to ZU, CA111842 to JP), the Hungarian Science Fund (OTKA 68758 to GL) and Proyecto de Excelencia (P06-CTS-01555, to RJ) and by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Red HERACLES RD06/0009,Spain; to RJ) and the Intramural Research Program of the National Institute on Aging, NIH (to RDC).
- Calorie restriction
- Oxidative stress
ASJC Scopus subject areas
- Developmental Biology