Resveratrol Key Ingredient to Healthy Aging

In the natural environment, animals rarely reach the stage of senescence, proposing that the notion of aging is unique to humans. Representing 38.9 million people in the United States, one out of eight is 65 years or older.¹ A newborn today has the life expectancy of 75 years as a boy and 80 years as a girl (AOA, Department of Health and Human Services; CDC 2008). Life expectancy is the average total number of years a human anticipates to live, while life span is the maximum number of years a human can live defined by the observed age of death of the oldest human. The most recognizable oldest person, Jeanne Calment a French woman, lived to be 122.5 years.² With that being said, life span has remained unchanged, but life expectancy increased almost 30 years in the last century. Today, more than ever, individuals are invested in increasing the longevity of life to maximize not only the quantity of years lived, but the quality.

With an aging population, it is no wonder products promoting healthy aging are so highly sought after and have been vastly developed in recent decades. Due to increased expectations surrounding standards of living and improved productivity later in life, the marketplace has seen an increase in anti-aging offerings. In a market of information overload, it is important to prioritize and validate claims to promote a product. With evidence-based science, resveratrol is no stranger to nutraceuticals and the anti-aging discussion.

Discovered almost seven decades ago, resveratrol (3, 4, 5-trihydroxystilbene) is a polyphenolic phytoalexin produced naturally as a defense mechanism against environmental stressors by more than 70 species of plants most commonly in the root of Japanese Knotweed. It can be found as a fat-soluble cis- or trans- isomer, the latter demonstrating more stability. Its bioavailability varies vastly if one consumes it or absorbs it under the tongue, the latter being more bioavailable.³ Trans-Resveratrol-3-O-glucuronides are the most common metabolites found in the plasma after administration. Administrating Resveratrol directly underneath the tongue allows for diffusion directly into the venous circulation. This advantage avoids the challenges of (1) having to be absorbed in the digestive system and (2) subsequent reduction by the liver before actual entrance into systemic circulation.

The popularity of resveratrol stemmed from its abundance in grapevines (Vitis vinifera) used to make red wine.⁴ Subsequent discussion has strongly suggested resveratrol accompanied by flavonoids (i.e. proanthocyanidins) and other polyphenols found in a full spectrum of grape extract and fermentation process in red wine contribute to The French Paradox. This concept has been suggested to explain the relatively high saturated fat-laden diet in France with yet relatively low incidence and prevalence of cardiovascular disease as compared to the United States.⁵

Although the rich source of resveratrol and other polyphenol compounds in red wine is enthusiastically promoted, one cannot consume enough resveratrol with moderate consumption of red wine. This reality has already ignited investments by pharmaceutical and nutraceutical companies to study and produce pure and stable extracts to provide suggested beneficial levels. It is no wonder resveratrol is among the top 10 anti-aging developments of the last three years and continues to be studied.

What makes resveratrol stand alone in its contribution to slowing the aging process and its potential role in healthy aging? Below are three ways in which resveratrol works to either promote processes in the body associated with healthy aging or inhibit responses that can lead to cell damage or death.

Caloric Restriction: This theory is a non-genetic approach defined by the reduction in caloric intake while maintaining essential requirements. Metabolic reprogramming to reduce energy metabolism and increase biosynthesis and turnover of proteins explain this theory through animal and human pathological studies. The Okinawan population consisting of the greatest percentage of centenarians in the world follows a diet similar to the caloric restriction theory⁶ (less caloric intake then the rest of Japan by about 20 percent and the United States by about 40 percent). By genetically determining the link and regulation of this theory, initial work by Dr. David Sinclair and his team paved the way when resveratrol was shown to be a sirtuin activator.^{7, 8,9,10} As a sirtuin activator, resveratrol has been suggested to mimic the action of the silent information regulator 2 [Sir2] to extend the lifespan in yeast and C. Elegans.⁷ The specific mechanism is still unclear, but has been suggested to modulate the mitochondrial respiratory chain (energy production) that mimics the caloric restriction theory.^{11,12,13,14,15}

Antioxidant: The accumulation of endogenous oxygen radicals not only activates damage to significant cell structures (e.g. mitochondria), but may also activate a cascade of oxidized proteins contributing to the age-related imbalance between free radicals and endogenous antioxidants. Resveratrol is considered a polyphenol and not only has demonstrated antioxidant characteristics, but also has been shown to work either synergistically and/or additively with flavonoids and other polyphenols.^16,17,18,19

Anti-Inflammatory: Acute as well as chronic inflammation activates a series of reactions with the eventuality of damage to tissue and cell death. It has been well documented that oxidation is a major cause of inflammation. Resveratrol has been shown to modulate pro-inflammatory factors directly and indirectly by maintaining redox homeostasis.^19,20,21

What has been suggested, demonstrated and continues to be explored can be utilized in a variety of practical applications. Due to resveratrols multiple modes of entry into the body, its formulation potential in beneficial products is vast. Resveratrol makes its mark from potential topical applications (e.g. creams/lotion, cosmetics and face mask) to functional food/beverages (e.g. chewing gum, nutritional bars, cookies, fruit snack chews and juice blend, tea infusions, on-the-go pre-package powder mixes and sport drinks). Manufacturers can even explore developing pure extracts supplements with considerations of other modes of entry (e.g. suppositories, transdermal adhesion patches and nasal mists).

Aging is a multi-factorial process and it is impossible to simplify aging as a notion of disease to be treated by a magic bullet. Aging no longer is defined by the wrinkles on ones face (thanks to ever-popular Botox injections), but rather aging is the transition to a stage in life involving susceptibility to disease and conditions compromising day-to-day living, with the eventuality of death. Of course, due to the predisposition of genetics, we cannot deny the expected natural progression of aging, nor should we. With that consideration of biological limitation, however, it is now increasingly recognized that nutrition beyond the basic recommendations plays an advantageous role in optimal living in other words, promoting healthy aging.

Anh Thu V. Tran, MS, MD is a nutrition consultant for Cyvex Nutrition.

Editors Note: References listed on the next page.

References:

1. Meyer, J., Age: 2000, Census 2000 brief. U.S. Department of Commerce, Economics and Statistical Administration, U.S. Census Bureau, 2001: http://www.census.gov/prod/2001pubs/c2kbr01-12.pdf

2. Allard M, et al. Jeanne Calment: From Van Goshs time to ours, 122 extraordinary years, Thorndike Press, 1999.

3. Marier JF et al., Metabolism and disposition of Resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidence by a linked-rat model. J Pharmacol Exp Ther, 2002; 302:369-73.

4. Pereira V et al., HPLC-DAD methodology for the quantification of organic acids, furans and polyphenols by direction of wine samples. J Sep Sci, 16 March 2010. [Epub ahead of print].

5. Lekli I et al., Longevity nutrients Resveratrol, wines and grapes. Genes Nutr, 2009 Sept 4. [Epub ahead of print].

6. Hokama T and Binns C., Declining longevity advantage and low birthweight in Okinawa. Asia Pac J Pacific Health, 2008; 20:95-101.

7. Howitz KT, et al., Small molecules activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature, 2003; 425:191-196.

8. Wood JG., et al., Sirtuin activators mimic caloric restriction and delay aging in metazoans. Nature, 2004; 430:686-9.

9. Baur JA et al., Resveratrol improves health and survival of mice on a high-caloric diet. Nature 2006; 444:337-42.

10. Baur JA et al., Therapeutic potential of Resveratrol: the in vivo evidence. Nature Reviews Drug Discovery, 2006; 5:493-506.

11. Allard J, et al. Dietary Activators of Sirt1. Mol Cell Endocrinol. 2009; 299: 58-63.

12. Valenzano DR et al., Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Current Bio, 2006; 16: 296-300.

13. Han SH. Potential Role of Sirtuin as a Therapeutic Target for Neurodegenerative Diseases. J Clin Neurol. 2009; 5:120-125.

14. Morselli E, et al. Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol. Aging. 2009; 1: 961-970.

15. Imai S. A possibility of nutriceuticals as an anti-aging intervention: Activation of sirtuins by promoting mammalian NAD biosynthesis. Pharmacol Res. 2010 January 18. [Epub ahead of print].

16. Mikulski D, et al. Quantitative structure-antioxidant activity relationship of trans-resveratrol oligomers, trans-4,4-dihydroxystilbene dimer, trans-resveratrol-3-O-glucuronide, glucosides: Trans-piceid, cis-piceid, trans-astringin and trans-resveratrol-4-O-beta-D-glucopyranoside. Eur J Med Chem, 2010 February 12. [Epub ahead of print].

17. Sebai H, et al. Resveratrol, a red wine polyphenol, attenuates lipopolysaccharide-induced oxidative stress in rat liver. Ecotoxicol Environ Saf. 2010 January 18. [Epub ahead of print].

18. Camont L, et al. Liquid chromatographic/electrospray ionization mass spectrometric identification of the oxidation end-products of trans-resveratrol in aqueous solutions. Rapid Commun Mass Spectrom. 2010; 24:634-42.

19. Lee EO, et al. Resveratrol reduces glutamate-mediated monocyte chemotactic protein-1 expression via inhibition of extracellular signal-regulated kinase ½ pathway in rat hippocampal slice cultures. J Neurochem. 2009 December 28. [Epub ahead of print]. 

20. Abraham J and Johnson RW., Consuming a diet supplemented with Resveratrol reduced infection-related neuroinflammation and deficits in working memory in aged mice. Rejuvenation Res, 2009; 12:445-53.

21. Wendeburg L et al., Resveratrol inhibits prostaglandin formation in IL-1 beta-stimulated SK-N-SH neuronal cells. J Neuroinflammation, 2009; 6:26.