Effects of resveratrol on aging: in vitro and in vivo studies

As the world population is increasingly aging, it is important to identify protective interventions aimed to reduce the deleterious effects of aging. Resveratrol is a stilbene compound produced by different plants, and red wine is the main source in the human diet. An anti-aging activity of resveratrol has been demonstrated in organisms ranging from yeasts to mammals (Howitz K.T. et al., 2003; Baur J.A. et al., 2006). The aim of this work was to further study the anti-aging activity of resveratrol in vitro using human fibroblasts in culture, and in vivo in mice. In vitro we observed that resveratrol, at concentrations in the micromolar range, delayed the onset of replicative senescence, and exerted protective effects on DNA oxidative damage, resistance to in vitro induced oxidative stress, and on age-associated changes such as increased nuclear DNA content and nuclear size. Global transcriptional changes were also evaluated by genome-wide gene expression microarray analysis. Resveratrol treatment had specific effects on the transcriptional profile of senescent fibroblasts, turning off complement and coagulation cascades and other innate immune response components typically activated during wound repair processes. Furthermore, resveratrol re-induced the basal expression of genes controlling cell cycle and DNA replication, down-regulated during aging. For the in vivo study, male C57Bl6 mice were fed from age 12 months to senescence a 10% fat diet containing resveratrol (22 mg/kg b.w.) or not. The lipid component was provided by extra-virgin olive (EVOO). An additional group fed EVOO with high antioxidant phenol content (H-EVOO) was also evaluated. The measured endpoints were biochemical parameters related to oxidative stress and functional tests to evaluate motor, cognitive and emotional behaviour. The main findings obtained in this study were an increase in muscular strength as measured in the grip strength test, and an amelioration in the performance on the rotarod, indicating improvement in motor coordination, found in both the resveratrol and H-EVOO groups. These data show that resveratrol and olive oil phenols share some interesting health-promoting effects in aging rodents. Future development of this work will include the evaluation in mice tissues of the changes in the gene expression pattern using whole-genome microarray.