Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No. 4 • August 2012

Why is [it] that nobody understands me, and everybody likes me?

— Albert Einstein, in an interview in The New York Times, 3/12/1944

(D&S: Could this be the FACEBOOK question of the century?)

Chronic Intake of Red Wine Polyphenols By Young Rats Protects Against Aging-Induced Decline in Physical Performance and Endothelial Dysfunction

After our discussion (see last issue of this newsletter) of a study in which people displayed increased creativity as a result of consuming alcohol to reach 0.07 blood level (a little less than the 0.08 level set for legally drunk), you may be thinking “uh oh, here we go again.” But, no, this study1 involved the consumption of powdered French red wine POLYPHENOLS (RWP), with small amounts of alcohol as solvent. One liter of red wine was said to produce 2.9 grams of phenolic extract, which contained 471 mg/g of total phenolic compounds expressed as gallic acid equivalent.1

The rats were divided into four groups that received the following treatments: controls (3% ethanol, solvent), RWPs at 25 mg/kg/day in 3% ethanol, RWPs at 75 mg/kg/day in 3% ethanol and a group receiving RWPs at 100 mg/kg/day in 3% ethanol plus apocynin (an antioxidant and inhibitor of NADPH oxidase, an enzyme that is a causative factor in some diseases by being a major source of oxidative stress. The researchers note that “[t]hese treatments correspond to human equivalent doses of 284, 851, and 1135 mg [of the RWP]., respectively, for a 70 kg. adult.” The solvent, RWPs and apocynin were given to the rats in their drinking water starting at week 16 until week 40.

As the authors explain, “[v]ascular aging appears to be initiated by an increased oxidative stress involving superoxide anions, which, in turn, inactivate NO [nitric oxide].” [Adequate amounts of NO are critical for vasodilatory function in blood vessels.] “Potential sources of superoxide anions in old arteries include NADPH oxidase, mitochondrial respiration chain, xanthine oxidase, and uncoupled eNOS.” In this paper,1 the authors observed that aging in their subject mice was associated with blunted endothelium-dependent relaxations, oxidative stress, and an upregulation of eNOS [endothelial nitric oxide synthase] and arginase. (Arginase is an enzyme that competes with eNOS for arginine and, when levels of arginase are increased, it can reduce the availability of arginine for the synthesis of nitric oxide by eNOS). Insufficient availability of arginine can induce the uncoupling of eNOS (resulting in the generation of superoxide anions instead of nitric oxide). These are all changes linked to endothelial dysfunction.

NADPH Oxidase Involved in Endothelial Dysfunction Accompanying Aging

Indicating that the enzyme NADPH oxidase was involved in the age-associated endothelial dysfunction was the increase with aging in the NADPH oxidase p22phox and nox1 subunits, combined with the improvement in endothelial dysfunction derived by the mice receiving the NADPH oxidase inhibitor apocynin. (The supplementation with RWPs also resulted in improved endothelial function.) “Regular administration of either RWPs (25 and/or 75 mg./kg./day) or apocynin (100 mg./kg./day) in the drinking water from week 16 until week 40 improved the aging-induced impairment of both the NO and the EDHF-mediated component of the relaxation to ACh [acetylcholine].”1 Moreover, “[i]ntake of either RWPs (25 and 75 mg./kg./day) or apocynin (100 mg/kg/day) prevented the aging-induced vascular oxidative stress and normalized the expression of eNOS and peroxynitrites.”1

Improvement in Physical Performance

The researchers kept track of the physical capabilities of the mice by assessing endurance capacity on a treadmill. Unsurprisingly, they observed a decrease in physical performance on the treadmill as a result of aging, with the old rats having an endurance capacity of 6.0 ± 0.6 min. as compared to 16.7 ± 0.9 min. for the young rats. “The aging-related physical impairment is partially but significantly improved by the RWPs treatment at a dose of 75 mg/kg/day (9.9 ± 1.3 min., n=6) but not 25 mg./kg./day (5.2 ± 1.0 min., n=4), and also by the apocynin treatment (10.9 ± 1.1 min., n=5).”1 The improvement with apocynin indicates that NADPH oxidase played an important role in the decreased vascular response with aging as a source of superoxide anions. Uncoupled eNOS is another source of superoxide anions in old arteries.


  1. Dal-Ros et al. Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: role of NADPH oxidase. Biochem Biophys Res Commun 404:743-749 (2011)

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