Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults.
BACKGROUND
Resveratrol, a plant-derived polyphenol, has been reported to improve glucose metabolism and vascular function and to extend life span in animal models, but studies in humans have been inconclusive.


METHODS
In a randomized, double-blind crossover study, we treated older glucose-intolerant adults (n = 30) with resveratrol (2-3 g/daily) or placebo, each for 6 weeks. A standard mixed-meal test was used to assess insulin sensitivity (Matsuda index) and secretion (C-peptide deconvolution) and vascular function by reactive hyperemia peripheral arterial tonometry. Skeletal muscle samples were obtained for gene expression using RNA-Seq analysis and to assess mitochondrial morphology.


RESULTS
There were no changes in glucose tolerance, insulin sensitivity, weight, blood pressure, or lipid profile following resveratrol treatment. Fasting reactive hyperemia index improved with resveratrol (2.02 ± 0.2 vs 1.76 ± 0.02, p = .002). RNA-Seq analysis yielded 140 differentially expressed transcripts (corrected p-value ≤ .05), predominantly associated with mitochondrial genes and noncoding RNA. Ingenuity Pathway Analysis confirmed that mitochondrial dysfunction (p = 2.77 × 10-12) and oxidative phosphorylation (p = 1.41 × 10-11) were the most significantly perturbed pathways. Mitochondrial number, but not size, was increased.


CONCLUSIONS
Resveratrol treatment of older adults with impaired glucose regulation may have beneficial effects on vascular function, but not glucose metabolism or insulin sensitivity. Changes in gene expression suggest effects similar to those observed with caloric restriction, which has been shown to increase life and health span in animal models, although its significance for humans is uncertain. Future human studies should address the appropriate dose range and low bioavailability of resveratrol.
Albert Einstein College of Medicine, Bronx, New York.
Rena M
RM
Pollack
Albert Einstein College of Medicine, Bronx, New York.
Nir
N
Barzilai
Albert Einstein College of Medicine, Bronx, New York.
Valentin
V
Anghel
Albert Einstein College of Medicine, Bronx, New York.
Ameya S
AS
Kulkarni
Albert Einstein College of Medicine, Bronx, New York.
Aaron
A
Golden
National University of Ireland Galway, Galway, Ireland.
Pilib
P
O'Broin
Harvard Medical School, Boston, Massachusetts.
David A
DA
Sinclair
Harvard Medical School, Boston, Massachusetts.
Michael S
MS
Bonkowski
Stanford University, Palo Alto, California.
Alexander J
AJ
Coleville
Albert Einstein College of Medicine, Bronx, New York.
Danielle
D
Powell
Albert Einstein College of Medicine, Bronx, New York.
Sharon
S
Kim
National Institute on Aging, Baltimore, Maryland.
Ruin
R
Moaddel
Albert Einstein College of Medicine, Bronx, New York.
Daniel
D
Stein
Albert Einstein College of Medicine, Bronx, New York.
Kehao
K
Zhang
Albert Einstein College of Medicine, Bronx, New York.
Meredith
M
Hawkins
Albert Einstein College of Medicine, Bronx, New York.
Jill P
JP
Crandall
D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008660:Metabolism / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D013267:Stilbenes; D005947:Glucose; D000077185:Resveratrol
Aging; Gene expression; Polyphenols; Prediabetes