Calorie restriction (CR) delays age-related diseases in laboratory animals, and a small molecule that safely mimics its effects has been greatly sought after. There is evidence that resveratrol can mimic effects of CR in lower organisms and we have now concluded the first study of the aging intervention program. In mice, we found that resveratrol induces gene expression patterns in multiple tissues that are highly similar to those induced by CR. Moreover, elderly resveratrol-fed mice showed a marked reduction in signs of aging. These changes included reduced albuminuria, decreased inflammation and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preservation of bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at mid-life. Thus it is possible to mimic transcriptional aspects of DR and delay functional decline with a safe, orally available small molecule. Our findings indicate that resveratrol treatment starting from mid-life has a range of beneficial effects in mice, but suggest that it may not be an effective strategy to increase the longevity of normal ad libitum-fed animals. Long-term resveratrol treatment mimicked important physiological and transcriptional aspects of CR in vivo, and allowed treated animals to live healthier, more vigorous lives. In addition to improving insulin sensitivity and increasing survival in mice fed a high calorie diet, we found evidence that resveratrol improves cardiovascular function, bone density, motor coordination, and delays cataracts, even in non-obese rodents. Since cardiovascular disease is a major cause of age-related morbidity and mortality in humans but not mice, it is possible that a CR mimetics such as resveratrol could have an even greater impact on human health than on mice. However, resveratrol does not seem to mimic all of the salutary effects of DR in that its introduction into the diet of normal one year old mice did not increase longevity.
| Gokarn, Rahul; Solon-Biet, Samantha M; Cogger, Victoria C et al. (2018) Long-term Dietary Macronutrients and Hepatic Gene Expression in Aging Mice. J Gerontol A Biol Sci Med Sci : |
| Gutiérrez-Casado, Elena; Khraiwesh, Husam; López-Domínguez, José A et al. (2018) The impact of aging, calorie restriction and dietary fat on mitochondrial ultrastructure, dynamics and autophagy markers in mouse skeletal muscle. J Gerontol A Biol Sci Med Sci : |
| Kane, Alice E; Huizer-Pajkos, Aniko; Mach, John et al. (2017) A Comparison of Two Mouse Frailty Assessment Tools. J Gerontol A Biol Sci Med Sci 72:904-909 |
| Westbrook, Reyhan M; Yang, Huan Le; Langdon, Jackie M et al. (2017) Aged interleukin-10tm1Cgn chronically inflamed mice have substantially reduced fat mass, metabolic rate, and adipokines. PLoS One 12:e0186811 |
| Navas-Enamorado, Ignacio; Bernier, Michel; Brea-Calvo, Gloria et al. (2017) Influence of anaerobic and aerobic exercise on age-related pathways in skeletal muscle. Ageing Res Rev 37:39-52 |
| Mercken, Evi M; Capri, Miriam; Carboneau, Bethany A et al. (2017) Conserved and species-specific molecular denominators in mammalian skeletal muscle aging. NPJ Aging Mech Dis 3:8 |
| von Loeffelholz, Christian; Lieske, Stefanie; Neuschäfer-Rube, Frank et al. (2017) The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism. Hepatology 66:616-630 |
| Fernández-Del-Río, Lucía; Nag, Anish; Gutiérrez Casado, Elena et al. (2017) Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor. Free Radic Biol Med 110:176-187 |
| Wahl, Devin; Coogan, Sean Cp; Solon-Biet, Samantha M et al. (2017) Cognitive and behavioral evaluation of nutritional interventions in rodent models of brain aging and dementia. Clin Interv Aging 12:1419-1428 |
| Ingram, Donald K; de Cabo, Rafael (2017) Calorie restriction in rodents: Caveats to consider. Ageing Res Rev 39:15-28 |
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