Resveratrol’s Antiaging, Brain-Boosting Potential

By Dr. Diane Fulton

A natural polyphenol, resveratrol has the potential to bring you longevity and protection against brain diseases. Why not try this age-defying compound?

Resveratrol is a polyphenol naturally present in grape skins, berries, peanuts and red wine that possesses anti-inflammatory, neuroprotective[i] and antiaging properties.[ii] Foods rich in polyphenols like resveratrol protect against age-related diseases, such as cardiovascular disease,[iii] cancers,[iv],[v],[vi] arthritis,[vii] cataracts,[viii] osteoporosis,[ix],[x] Type 2 diabetes,[xi],[xii] high blood pressure,[xiii] pulmonary disease,[xiv] atherosclerosis[xv] and Alzheimer’s disease (AD).[xvi]

Resveratrol can influence multiple inflammatory and non-inflammatory responses, protecting organs and tissues, thanks to its interaction with immune cells and its activity on a protein called Sirtuin 1 (SIRT1), which is tied to inflammatory, metabolic and oxidative stressors.[xvii]


Resveratrol has been shown to mediate antiaging effects through modulation of many different pathways. It will bind to numerous cell-signaling molecules, activate various transcription factors, suppress the expression of antiapoptotic gene products, inhibit protein kinases, induce antioxidant enzymes, suppress the expression of inflammatory biomarkers, inhibit the expression of angiogenic and metastatic gene products and modulate cell cycle regulatory genes, which makes it a powerhouse against numerous age-associated diseases.[xviii]

Resveratrol and pterostilbene, the polyphenols found in grapes and blueberries, have beneficial effects as antiaging compounds through modulating the hallmarks of aging — oxidative damage, inflammation, telomere shortening and cell senescence. Both resveratrol and pterostilbene are linked to possible aging biomarkers — oxidative stress, inflammation and high-calorie diets — and have the potential to improve lifespan, prevent aged-related diseases and maintain health.[xix]

In a study of 125 postmenopausal women, aged 45 to 85 years, who took 75 milligrams (mg) of trans-resveratrol or placebo twice daily for 12 months and then crossed over to the alternative treatment for another 12 months, results show resveratrol has powerful antiaging and health effects.

Compared to placebo, resveratrol supplementation resulted in a 33% improvement in overall cognitive performance, and a relative improvement in verbal memory among women 65 and older was found, compared to those younger than 65 years. Regular supplementation with low-dose resveratrol showed positive impacts on cognition, cerebrovascular function and insulin sensitivity in postmenopausal women.[xx]

Using human skin tissue, researchers reported the presence of specific resveratrol binding sites in the epidermis of the skin. Exposure of these cells to the nitric oxide free radical donor sodium nitroprusside (SNP) resulted in cell death, which was significantly reduced by resveratrol at 14.7 micron (µM).

The protective action of resveratrol is related to its ability to reduce both the number of apoptotic cells as well as mitochondrial apoptotic events triggered by SNP. Resveratrol may be useful to prevent skin diseases.[xxi]

Menopause often increases age-related skin changes and leads to accelerated skin aging. Through in vitro study of menopausal women’s skin fibroblasts, cells treated with resveratrol either alone or combined with N-acetyl-L-cysteine (NAC) in doses of 10, 100 or 1,000 μM resulted in a dose-related increase in the rate of cell proliferation and inhibition of collagenase activity, thus improving skin elasticity and collagen production resulting in more youthful looking skin.[xxii]

E-Course: Herbal Energetics (Ad)

In a trial of 60 community-dwelling adults 55 to 78 years old with functional limitations, three groups were equally divided into those who exercised with placebo, those who exercised with 500 mg per day of resveratrol or those who exercised with 1,000 mg per day of resveratrol. Exercise consisted of two sessions a week of center-based walking and whole-body resistance training for 12 weeks.

Physical function showed marked and dose-related improvements in gait speed and the six-minute walk test as well as the most improved skeletal muscle mitochondrial function for citrate synthase and cytochrome C oxidase (COX) activity with the larger dose of resveratrol combined with exercise.[xxiii]

At a dose of 5 micromolar, which is pharmacologically relevant and 20 times lower than previously published concentrations, resveratrol significantly extended the worm C. elegans mean and maximum lifespan by 3.6% and 3.4% respectively, showing resveratrol’s ability to promote longevity.[xxiv]

Brain Boosting

The prevalence of neurodegenerative disorders characterized by loss of neuronal function is rapidly increasing. In a systematic review of resveratrol treatment of neurodegenerative disorders, resveratrol successfully reduced cell damage due to inflammation and modulated cellular processes, including autophagy and the apoptosis cascade under stress.

Autophagy means “self-eating” and refers to detoxing of parts of your cells without damaging tissues around them.[xxv] Apoptosis means “falling away” or what is called a “programmed cell death,” which cleans out cells that are not serving the body well such as disposing of pre-cancerous cells, infected cells and cells with growth abnormalities.[xxvi],[xxvii] Current evidence supports the beneficial effects of resveratrol as a therapy for neurodegenerative disorders.[xxviii]

Resveratrol impacts pathological mechanisms of debilitating neurological disorders, such as stroke,[xxix] ischemia,[xxx] Huntington’s disease,[xxxi],[xxxii] Parkinson’s disease[xxxiii] and AD.[xxxiv] Emerging literature indicates that mechanisms of aging and AD are intricately linked[xxxv] and that these mechanisms can be modulated with resveratrol as shown in animal, in vitro and human studies.[xxxvi],[xxxvii]

In a retrospective study, scientists examined banked cerebrospinal fluid (CSF) and plasma samples from 38 mild to moderate AD subjects with CSF Aβ42 below 600 nanograms per milliliter (ng/ml) — a biomarker used to confirm AD — at baseline for two equal-sized groups — resveratrol-treated and placebo-treated with a 1-gram pill twice daily for 52 weeks.

Resveratrol significantly reduced CSF metalloproteinases (MMPs), modulated neuroinflammation markers, induced adaptive immunity and improved activities of daily living scores for the treated group compared to the placebo.[xxxviii]

Oxidative damage is often involved in the pathophysiology of age-related ailments such as AD. Studies of brain tissue and lymphocytes from AD patients show increased reactive oxidative species (ROS) compared to healthy controls. In a human in vitro study of the lymphoblastoid cell lines from AD and healthy patients, resveratrol triggered a protective response against ROS under control and oxidizing conditions and increased the expression of genes encoding known antioxidants and antiaging factors in both groups studied.[xxxix]

In a mouse model of Huntington’s disease, resveratrol-induced SIRT1 was found to protect neurons against ployQ toxicity — which leads to neurons dying — and induced-Wallerian degeneration — from cutting or crushing a nerve fiber — in experimental mice, and protect neurons from axotomy — disruption of the neurons’ cell impulse process. Resveratrol may possess therapeutic value to neuronal degeneration.[xl]

In a metal-induced rat model of neurodegenerative disease, six natural compounds — caffeine, gallic acid, resveratrol, epigallocatechin gallate, vitamin C and vitamin E — were all found to decrease heavy metal-induced cell damage in rats. These compounds reduced the heavy metal effects on apoptosis, necrosis and ROS levels and were regulated by mitochondrial protein changes. These natural compounds have therapeutic potential against heavy metal toxicity-induced neurodegenerative diseases due to their neuroprotective properties.[xli]

Memory impairment is another neurological disorder that resveratrol could impact.[xlii] In a rat model study, resveratrol improved induced-spatial learning memory impairment.[xliii] In a study of resveratrol in aging mice, treatment preserved cognitive function and led to higher microvascular density and a lower number of microvascular abnormalities in comparison to aging non-treated control animals. Resveratrol seems to promote cognitive function and brain health during aging.[xliv]

Age-Defying and Neuro-Health Benefits

Resveratrol is a natural compound that may boost your brain health and help you look younger, live longer and function at a higher level as you age. For more research on this amazing substance, please see’s scientific evidence on resveratrolneurodegenerative diseases and aging.


[i] Lange, K.W. and Li, S. (2018), Resveratrol, pterostilbene, and dementiaBioFactors, 44: 83-90.

[ii] Kalantari, H. and Das, D.K. (2010), Physiological effects of resveratrol. BioFactors, 36: 401-406. [iii] Giuseppe Annunziata, Maria Maisto, Connie Schisano, Roberto Ciampaglia, Viviana Narciso, Gian Carlo Tenore, Ettore Novellino. Effects of Grape Pomace Polyphenolic Extract (Taurisolo) in Reducing TMAO Serum Levels in Humans: Preliminary Results from a Randomized, Placebo-Controlled, Cross-Over Study. Nutrients. 2019 Jan 10 ;11(1). Epub 2019 Jan 10. PMID: 30634687 [iv] Ketan R Patel, Victoria A Brown, Donald J L Jones, Robert G Britton, David Hemingway, Andrew S Miller, Kevin P West, Tristan D Booth, Marjorie Perloff, James A Crowell, Dean E Brenner, William P Steward, Andreas J Gescher, Karen Brown. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Antiviral Res. 2008 Feb;77(2):153-6. Epub 2007 Oct 8. PMID: 20841478 [v] Yulan Lin, Agneta Yngve, Jesper Lagergren, Yunxia Lu. A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer. Br J Nutr. 2014 Dec ;112(12):2002-9. Epub 2014 Oct 27. PMID: 25345471 [vi] Arindam Mondal, Lunawati L Bennett. Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP cleavage. Biomed Pharmacother. 2016 Dec ;84:1906-1914. Epub 2016 Nov 15. PMID: 27863838 [vii] Mehdi Shakibaei, Constanze Buhrmann, Ali Mobasheri. Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappaB ligand (RANKL) activation of NF-kappaB signaling and inhibit osteoclastogenesis in bone-derived cells. J Biol Chem. 2011 Jan 14. Epub 2011 Jan 14. PMID: 21239502 [viii] Amrita Singh, Surendra H Bodakhe. Resveratrol delay the cataract formation against naphthalene-induced experimental cataract in the albino rats. J Biochem Mol Toxicol. 2019 Nov 20:e22420. Epub 2019 Nov 20. PMID: 31746523 [ix] Z P Liu, W X Li, B Yu, J Huang, J Sun, J S Huo, C X Liu. Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the ovariectomized rat model. J Med Food. 2005 Spring;8(1):14-9. PMID: 15857203 [x] Zihan Wang, Le Li, Wenwen Gu, Yuqi Mao, Tao Wang. Resveratrol Reverses Osteogenic Decline of Bone Marrow Mesenchymal Stem Cells via Upregulation of YAP Expression in Inflammatory Environment. Stem Cells Dev. 2021 Oct 1. Epub 2021 Oct 1. PMID: 34598655 [xi] Ahmad Zare Javid, Razie Hormoznejad, Hojat Allah Yousefimanesh, Mohammad Hosein Haghighi-Zadeh, Mehrnoosh Zakerkish. Impact of resveratrol supplementation on inflammatory, antioxidant, and periodontal markers in type 2 diabetic patients with chronic periodontitis. Diabetes Metab Syndr. 2019 Jul – Aug;13(4):2769-2774. Epub 2019 Jul 24. PMID: 31405706 [xii] Pál Brasnyó, Gergő A Molnár, Márton Mohás, Lajos Markó, Boglárka Laczy, Judit Cseh, Esztella Mikolás, István András Szijártó, Akos Mérei, Richárd Halmai, László G Mészáros, Balázs Sümegi, István Wittmann. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011 Mar 9:1-7. Epub 2011 Mar 9. PMID: 21385509 [xiii] Oli Sarkar, Yuan Li, Madhu B Anand-Srivastava. Resveratrol prevents the development of high blood pressure in spontaneously hypertensive rats through the inhibition of enhanced expression of Giα proteins. Can J Physiol Pharmacol. 2019 Mar 29. Epub 2019 Mar 29. PMID: 30925226 [xiv] Xiao-Ju Liu, Hai-Rong Bao, Xiao-Li Zeng, Jun-Ming Wei. Effects of resveratrol and genistein on nuclear factor-κB, tumor necrosis factor-α and matrix metalloproteinase-9 in patients with chronic obstructive pulmonary disease. Mol Med Rep. 2016 Mar 28. Epub 2016 Mar 28. PMID: 27035424 [xv] Yuanqi Yang, Chuan Liu, Jie Yang, Fangzhengyuan Yuan, Ran Cheng, Renzheng Chen, Yang Shen, Lan Huang. Impairment of sirtuin 1-mediated DNA repair is involved in bisphenol A-induced aggravation of macrophage inflammation and atherosclerosis. Chemosphere. 2021 Feb ;265:128997. Epub 2020 Nov 18. PMID: 33239236 [xvi] Sara Sarroca, Alaó Gatius, Eduard Rodríguez-Farré, David Vilchez, Mercè Pallàs, Christian Griñán-Ferré, Coral Sanfeliu, Rubén Corpas. Resveratrol confers neuroprotection against high-fat diet in a mouse model of Alzheimer’s disease via modulation of proteolytic mechanisms. J Nutr Biochem. 2020 Dec 12:108569. Epub 2020 Dec 12. PMID: 33321185 [xvii] Alesci A, Nicosia N, Fumia A, Giorgianni F, Santini A, Cicero N. Resveratrol and Immune Cells: A Link to Improve Human Health. Molecules. 2022 Jan 10;27(2):424. doi: 10.3390/molecules27020424. PMID: 35056739; PMCID: PMC8778251. [xviii] Kuzhuvelil B Harikumar, Bharat B Aggarwal. Resveratrol: a multitargeted agent for age-associated chronic diseases. Cell Cycle. 2008 Apr 15;7(8):1020-35. Epub 2008 Feb 15. PMID: 18414053 [xix] Yi-Rong Li, Shiming Li, Chi-Chien Lin. Effect of resveratrol and pterostilbene on aging and longevity. Biofactors. 2017 Dec 6. Epub 2017 Dec 6. PMID: 29210129 [xx] Thaung Zaw JJ, Howe PR, Wong RH. Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study. Clin Nutr. 2021 Mar;40(3):820-829. doi: 10.1016/j.clnu.2020.08.025. Epub 2020 Aug 27. PMID: 32900519. [xxi] Stéphane Bastianetto, Yvan Dumont, Albert Duranton, Freya Vercauteren, Lionel Breton, Rémi Quirion. Protective action of resveratrol in human skin: possible involvement of specific receptor binding sites. PLoS One. 2010;5(9):e12935. Epub 2010 Sep 23. PMID: 20886076 [xxii] S Giardina, A Michelotti, G Zavattini, S Finzi, C Ghisalberti, F Marzatico. Efficacy study in vitro: assessment of the properties of resveratrol and resveratrol + N-acetyl-cysteine on proliferation and inhibition of collagen activity. Minerva Ginecol. 2010 Jun;62(3):195-201. PMID: 20595944 [xxiii]Sara A Harper, John R Bassler, Sujitha Peramsetty, Youfeng Yang, Lisa M Roberts, Devin Drummer, Robert T Mankowski, Christiaan Leeuwenburgh, Karina Ricart, Rakesh P Patel, Marcas M Bamman, Stephen D Anton, Byron C Jaeger, Thomas W Buford. Resveratrol and exercise combined to treat functional limitations in late life: A pilot randomized controlled trial. Exp Gerontol. 2020 Oct 14:111111. Epub 2020 Oct 14. PMID: 33068691 [xxiv] K Zarse, S Schmeisser, M Birringer, E Falk, D Schmoll, M Ristow. Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans. Horm Metab Res. 2010 Nov;42(12):837-9. Epub 2010 Oct 5. PMID: 20925017 [xxv] D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019 Jun;43(6):582-592. doi: 10.1002/cbin.11137. Epub 2019 Apr 25. PMID: 30958602. [xxvi] Naught, Justin (2019) I am Clovix, Difference Between Autophagy & Apoptosis – The Complex Link, [xxvii] Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007 Jun;35(4):495-516. doi: 10.1080/01926230701320337. PMID: 17562483; PMCID: PMC2117903. [xxviii] Mohammad Hossein Pourhanifeh, Rana Shafabakhsh, Russel J Reiter, Zatollah Asemi. The effect of resveratrol on neurodegenerative disorders: possible protective actions against autophagy, apoptosis, inflammation and oxidative stress. Curr Pharm Des. 2019 Jul 17. Epub 2019 Jul 17. 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Understanding the Role of Histone Deacetylase and their Inhibitors in Neurodegenerative Disorders: Current Targets and Future Perspective. Curr Neuropharmacol. 2022;20(1):158-178. doi: 10.2174/1570159X19666210609160017. PMID: 34151764. [xxxvi] Thimmappa S Anekonda. Resveratrol–a boon for treating Alzheimer’s disease? Brain Res Rev. 2006 Sep;52(2):316-26. PMID: 16766037 [xxxvii] Singh, AP, Singh, R, Verma, SS, et al. Health benefits of resveratrol: Evidence from clinical studies. Med Res Rev. 2019; 39: 1851- 1891. [xxxviii] Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, Aisen PS, Turner RS. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s disease. J Neuroinflammation. 2017 Jan 3;14(1):1. doi: 10.1186/s12974-016-0779-0. PMID: 28086917; PMCID: PMC5234138. [xxxix] Marta Cosín-Tomàs, Júlia Senserrich, Marta Arumí-Planas, Carolina Alquézar, Mercè Pallàs, Ángeles Martín-Requero, Cristina Suñol, Perla Kaliman, Coral Sanfeliu. Role of Resveratrol and Selenium on Oxidative Stress and Expression of Antioxidant and Anti-Aging Genes in Immortalized Lymphocytes from Alzheimer’s Disease Patients. Nutrients. 2019 Jul 31 ;11(8). Epub 2019 Jul 31. PMID: 31370365 [xl] Anekonda TS. Resveratrol–a boon for treating Alzheimer’s disease? Brain Res Rev. 2006 Sep;52(2):316-26. doi: 10.1016/j.brainresrev.2006.04.004. PMID: 16766037. [xli] Lina Yang, Keshu Shen, Dongping Ji. Natural compounds attenuate heavy metal-induced PC12 cell damage. J Int Med Res. 2020 Jun ;48(6):300060520930847. PMID: 32552232 [xlii] Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012 Feb 3;148(3):421-33. doi: 10.1016/j.cell.2012.01.017. PMID: 22304913; PMCID: PMC3431801. 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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.

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