Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults

Rena M. Pollack, Nir Barzilai, Valentin Anghel, Ameya S. Kulkarni, Aaron Golden, Pilib O'Broin, David A. Sinclair, Michael S. Bonkowski, Alexander J. Coleville, Danielle Powell, Sharon Kim, Ruin Moaddel, Daniel T. Stein, Kehao Zhang, Meredith A. Hawkins, Jill P. Crandall

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1703-1709
Number of pages7
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Volume72
Issue number12
DOIs
StatePublished - Nov 9 2017

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Blood Vessels
Glucose
Insulin Resistance
Hyperemia
Animal Models
RNA
Gene Expression
Caloric Restriction
Untranslated RNA
Mitochondrial Genes
C-Peptide
Oxidative Phosphorylation
Manometry
Polyphenols
Double-Blind Method
Cross-Over Studies
Biological Availability
Meals
resveratrol
Fasting

Keywords

  • Aging
  • Gene expression
  • Polyphenols
  • Prediabetes

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

Cite this

Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults. / Pollack, Rena M.; Barzilai, Nir; Anghel, Valentin; Kulkarni, Ameya S.; Golden, Aaron; O'Broin, Pilib; Sinclair, David A.; Bonkowski, Michael S.; Coleville, Alexander J.; Powell, Danielle; Kim, Sharon; Moaddel, Ruin; Stein, Daniel T.; Zhang, Kehao; Hawkins, Meredith A.; Crandall, Jill P.

In: The journals of gerontology. Series A, Biological sciences and medical sciences, Vol. 72, No. 12, 09.11.2017, p. 1703-1709.

Research output: Contribution to journalArticle

Pollack, Rena M. ; Barzilai, Nir ; Anghel, Valentin ; Kulkarni, Ameya S. ; Golden, Aaron ; O'Broin, Pilib ; Sinclair, David A. ; Bonkowski, Michael S. ; Coleville, Alexander J. ; Powell, Danielle ; Kim, Sharon ; Moaddel, Ruin ; Stein, Daniel T. ; Zhang, Kehao ; Hawkins, Meredith A. ; Crandall, Jill P. / Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults. In: The journals of gerontology. Series A, Biological sciences and medical sciences. 2017 ; Vol. 72, No. 12. pp. 1703-1709.
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abstract = "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.",
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AU - Pollack, Rena M.

AU - Barzilai, Nir

AU - Anghel, Valentin

AU - Kulkarni, Ameya S.

AU - Golden, Aaron

AU - O'Broin, Pilib

AU - Sinclair, David A.

AU - Bonkowski, Michael S.

AU - Coleville, Alexander J.

AU - Powell, Danielle

AU - Kim, Sharon

AU - Moaddel, Ruin

AU - Stein, Daniel T.

AU - Zhang, Kehao

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AU - Crandall, Jill P.

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N2 - 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.

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