Geroprotectors in anti-age therapy

Andrey Primak , functional medicine doctor, member of the American Academy of Anti-Aging Medicine, general director of Medicom blades (Ukraine, Kiev)

Geroprotectors (literally translated as “protecting against old age”) is a general name for a group of substances that have been found to have the ability to increase life expectancy. Experts have identified more than 20 substances that have this effect. In particular, geroprotectors include: antioxidants (vitamins A, E and C, carotenoids, lipoic acid, coenzyme Q, trace element selenium and others), succinic acid, protein biosynthesis inhibitors (olivomycin, actinomycin), hormones (growth hormone, thyroid hormones ), peptide bioregulators, biguanides, adaptogens (ginseng and eleutherococcus preparations).

Geroprotectors can be used at young and mature ages. However, the question of the safety of their long-term use still requires study. This is due to the fact that a number of geroprotectors, in addition to their positive effect on the body, also have pronounced side effects. Due to this circumstance, in our clinical practice we can use only those geroprotectors that are free of side effects.

Since studies on the effect of various drugs on human life expectancy have not been published, we can evaluate the effect of certain drugs on aging using indirect evidence. First of all, geroprotectors include drugs that reduce the risk of developing chronic diseases that shorten life expectancy, and at the same time do not have a negative impact on the risk of developing other pathological conditions. For example, while reducing the risk of cardiovascular diseases, they do not increase the risk of malignant neoplasms. Another way to assess the effect of drugs on aging may be to assess its effect on the parameters of aging in the body. The most objective and versatile marker for assessing aging in the body is the study of the stability of the human genome. The better the genome stability indicators, the lower the biological age of a person (20; 21; 22).

The fight against external manifestations of age creates only an external illusion. Although for many patients this is more important than other manifestations of old age. But, if external influences go in parallel with the interventions of anti-aging medicine, this makes it possible to achieve a more stable and long-lasting result. Therefore, there is a clear trend in the world to combine technologies that make it possible to quickly change the appearance of patients and technologies for reversing the aging process. Often these unions occur under the roof of the same clinic. And in this we see the future of anti-aging medicine and cosmetology

Geroprotectors that reduce the risk of developing chronic diseases

One of the immediate reasons for the reduction in human life expectancy is the early onset of chronic diseases, which can lead to premature death. Our genotype is designed for 120–140 years of life, but most of our compatriots do not live up to half of the life allotted to us, and the reason for this is primarily cardiovascular diseases, malignant neoplasms and other chronic conditions. In this regard, it would be logical to assume that the main task of geroprotectors is the effective prevention (treatment) of diseases that significantly reduce human life expectancy. These products include: green tea catechins, soy isoflavones, resveratrol, omega-3 fatty acids, aqueous garlic extract, turmeric extract, friendly intestinal flora, vitamin and mineral complexes.

Soy isoflavones are antioxidants that have weak estrogen-like effects, which is why they are also called phytoestrogens. Soy isoflavones have been shown to have positive effects on markers of cardiovascular disease in many double-double, placebo-controlled studies. Thus, they have the ability to reduce cholesterol and LDL (low-density lipoprotein) cholesterol (2), reduce LDL oxidation (3), reduce homocysteine levels (4), and increase both endothelium-dependent and endothelium-independent vasodilation (5). Soy isoflavones reduce the risk of malignant neoplasms. Thus, according to a large epidemiological study, the level of gynestein in the blood is inversely proportional to the risk of developing malignant neoplasms (6). The preventive effect of soy isoflavones against breast cancer (7), endometrial cancer (8), and prostate cancer (9) has also been noted. In addition, soy isoflavones increase bone density and reduce the risk of osteoporosis (10), improve cognitive function during menopause (11), and increase insulin sensitivity and reduce blood glucose concentrations (12). It should also be noted that soy isoflavones at a dose of 40 mg per day for 12 weeks improve the condition of the skin (reduce the severity of wrinkles and improve skin elasticity) in women aged 30–40 years (13).

Thus, soy isoflavones reduce the risk of cardiovascular diseases, malignant neoplasms, increase bone density, increase insulin sensitivity, improve cognitive function, improve the condition of the skin, i.e., inhibit the development of those pathological processes that are associated with aging of the body. You can start taking soy isoflavones from the age of 35. However, the usual dose of soy isoflavones does not exceed 90 mg per day. It is preferable to prescribe soy isoflavones to women before menopause (during perimenopause) and during menopause, patients with insulin resistance, men with endothelial dysfunction at high risk of developing prostate cancer.

Green tea catechins. Another nutraceutical that has a broad preventive effect against the development of pathological processes associated with aging of the body is green tea catechins. Green tea catechins reduce the risk of cardiovascular diseases by lowering cholesterol levels (14), inhibiting LDL oxidation (15), and improving endothelial function (16). High consumption of green tea catechins inhibits the development of malignant tumors. This is evidenced by a study that found that consuming more than 10 cups of green tea per day resulted in tumors appearing 8.7 years later in women and 3 years later in men, compared with a group of study subjects who consumed less than 3 cups per day (17). In addition, according to many scientific studies, green tea catechins have a preventive effect against the development of many forms of malignant neoplasms. Thus, catechins reduce the risk of breast cancer (18), ovarian cancer (19), colon and pancreatic cancer (20), esophageal cancer (23), and prostate cancer (24). In addition, green tea catechins improve cognitive function and inhibit the aging process of the brain (25), reduce the risk of developing type II diabetes (26), and increase bone density (27). The effect that green tea extract has on the condition of connective tissue and skin is very interesting. Epigallocatechin gallate has been found to reduce UV-induced skin damage by inhibiting matrix metalloproteases and inhibiting inflammation in the skin (28). The daily dose of green tea extract varies from 500 to 1,500 mg per day. Green tea catechins should be prescribed to patients with detoxification disorders, in particular, residents of large cities, in case of insolation, and with a family history of malignant neoplasms and cardiovascular diseases.

Omega-3 fatty acids are essential fatty acids that are necessary for the formation of cell membranes, the synthesis of prostaglandins, etc. Omega-3 fatty acids are an important structural component of the tissues of the central nervous system and the retina, they make up more than half of all fats that form these organs . Modern scientific research has shown that omega-3 fatty acids are a very effective means of preventing cardiovascular diseases. Thus, an Italian study found that consuming 1 gram of omega-3 fatty acids per day reduced overall mortality by 20%, cardiovascular mortality by 30%, and sudden coronary death by 45% (29). In addition, omega-3 fatty acids have anti-inflammatory effects (30), reduce sympathetic nervous system activity (31), increase insulin sensitivity, and improve type 2 diabetes (32). Also, these fatty acids have a preventive effect against the development of retinopathy (33), reduce the risk of suicide (34), improve the course of epilepsy (35), have a good therapeutic effect in patients with multiple sclerosis (36), and reduce the risk of allergies in children when taking them mother during pregnancy and breastfeeding (37). The therapeutic dose of omega-3 fatty acids varies from 700 to 1,500 mg per day. Omega-3 fatty acids are prescribed to patients at high risk of developing cardiovascular diseases, chronic inflammatory diseases, depression and other central nervous system diseases, as well as women taking hormonal medications, to prevent hypercoagulation.

Aqueous extract of garlic has such a comprehensive positive effect on the body that a number of authors consider it to be a fairly effective anti-age agent (38). First, it inhibits some aging mechanisms, such as glycosylation processes (39), and also stimulates detoxification capabilities (40) and antioxidant protection (41). Secondly, garlic extract reduces the risk of many chronic diseases that accompany the aging process in the body. For example, garlic extract reduces the risk of cardiovascular disease (42) through a variety of mechanisms, including by reducing blood clotting (43). In addition, garlic extract reduces the risk of developing malignant neoplasms in general (44) and stomach and colon cancer (45) in particular, as well as prostate cancer (46). Researchers also note that this substance reduces the risk of developing dementia and Alzheimer's disease (47). Garlic extract should be prescribed to patients with a high risk of malignant neoplasms, cardiovascular diseases, to prevent thrombosis, including those induced by taking hormonal drugs, to improve the detoxification capabilities of the body, as well as to patients with recurrent candidiasis.

Turmeric extract. Another remedy that has a comprehensive positive effect on the body is turmeric extract. Turmeric affects at least two mechanisms of aging:

• associated with “accumulation of waste”;
• associated with exposure to free radicals.

Experimental studies in animals have shown that turmeric both has strong antioxidant effects (48) and is a modulator of detoxifying enzymes in the body. Turmeric extract reduces the activity of phase I detoxification enzymes and stimulates the activity of phase II detoxification enzymes (49). Another well-known property of turmeric is its anti-inflammatory effect. Considering that systemic inflammation in the body is one of the important pathogenetic mechanisms of aging (50), this effect of turmeric may also underlie its anti-age effects. This multifaceted effect of turmeric makes it possible to consider it as an important therapeutic agent for the prevention of chronic inflammatory conditions and inflammation-related chronic diseases, such as dystrophic processes in the central nervous system, cardiovascular diseases, pulmonary diseases, autoimmune diseases and neoplasia (51). The daily dose of turmeric extract is 250–2,000 mg per day.

Resveratrol is a dark red antioxidant found in the skins of red grapes and peanuts. Interest in this antioxidant as a potential geroprotector arose when it was discovered that it has the ability to induce the expression of genes that are associated with longevity (SIRT-1). Resveratrol also has an antioxidant effect (52) and stimulates detoxification processes (53), which increases its geroprotective activity. Resveratrol has broad therapeutic effects against many chronic diseases. In particular, it has anticancer properties (54), inhibits the development of atherosclerosis (55), prevents the formation of beta-amyloid and reduces the severity of oxidative stress in the central nervous system (56), and increases insulin sensitivity (57). The therapeutic dose of resveratrol is 10–50 mg per day. It is prescribed to patients at high risk of cardiovascular diseases, malignant neoplasms, for the prevention of dementia and Alzheimer's disease, as well as to overweight patients to increase insulin sensitivity.

Geroprotectors that improve genome stability

In recent years, the number of studies aimed at studying the effect of various drugs on indicators of genome stability, an objective marker of aging of the body, has increased significantly. Despite the fact that these studies do not yet cover very large groups of subjects (up to 600 people), they nevertheless provide the first results about the means that stabilize our genome and thus inhibit the aging process. These studies showed that the following statistically significantly stabilize the genome: folic acid, a combination of folic acid and vitamin B12, β-carotene, coenzyme Q10, vitamin C + vitamin E, complex antioxidant (α-tocopherol, β-carotene, vitamin C, selenium or α -tocopherol, β-carotene, vitamin C, folic acid, rutin, retinol acetate), red wine polyphenols (58). The role of vitamins in maintaining genome stability is also very interesting. A US study of 586 women found that taking a daily multivitamin, B vitamins - but more so a combination of vitamins and antioxidants - statistically significantly increased telomere length.

Telomeres are the ends of chromosomes that protect them during cell division. They also contain a full set of enzymes that repair cell DNA damage. Therefore, the larger the chromosome size, the more stable the genome. But the most interesting thing is that if the patient takes vitamins less than 3 times a week (or, as we are used to taking them, in courses), then the telomere length in this group was less than in the group not taking multivitamins. The best telomere length parameters were obtained with daily intake of vitamins and antioxidants (59).

An unexpected hypothesis was proposed by a group of scientists who studied the effect of intestinal flora on the body. They found that friendly intestinal flora is the source of the synthesis of prolamines localized in the intestinal lumen. Prolamins have the ability to stabilize DNA, RNA and cell proteins, and also stimulate the process of autophagy, a process that is necessary to cleanse the cell of destroyed protein complexes, such as lipofuscin. Prolamins also help maintain normal intestinal barrier function, inhibit systemic inflammation, and have an antioxidant effect. These versatile effects inhibit the aging process in the body and promote longevity. Among the bacteria whose intake increases the synthesis of prolamines, the authors identify Bifidobacterium lactis and Lactobacillus acidophilus NCFM strain (60).

conclusions

Modern scientific research reveals to us a wide range of natural compounds that significantly slow down the aging process in the body. These include soy isoflavones, garlic extract, green tea catechins, curcumin, resveratrol, multivitamins and friendly microorganisms. The widespread use of these agents in clinical practice will likely not only significantly reduce the risk of chronic pathological conditions, but also significantly slow down the aging process in the face of a constantly deteriorating environmental condition.

Literature

1. Anisimov, V. N. Pharmacological agents that increase life expectancy. Chapter 9. St. Petersburg: Nauka, 2003.
2. R, Mackey, A, Ekangaki and JA., Eden. The effects of soy protein in women and men with elevated plasma lipids. . Biofactors. 2000, r., 12(1-4) p251-7.
3. TB, Clarkson and MS, Anthony. Phytoestrogens and coronary heart disease. Baillieres Clin Endocrinol Metab (England), . 12(4) p589-604., Dec 1998, r.
4. Nagata C; Shimizu H; Takami R; Hayashi M; Takeda N; Yasuda K. Soy product intake is inversely associated with serum homocysteine level in premenopausal Japanese women. J Nutr (United States), Mar 2003, 133(3) p797-800.
5. Lissin LW; Oka R; Lakshmi S; Cooke J.P. Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia. Vasc Med , Feb 2004, 9(1) p26-30.
6. Ravindranath MH; Muthugounder S; Presser N; Viswanathan S. Anticancer therapeutic potential of soy isoflavone, genistein. Adv Exp Med Biol, 2004, 546 p121-65.
7. Linseisen J; Piller R; Hermann S; Chang-Claude J. Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study. Int J Cancer (United States), Jun 10 2004, 110(2) p284-90.
8. Xu WH; Zheng W; Xiang YB; Ruan ZX; Cheng JR; Dai Q; Gao YT; Shu XO. Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study. BMJ (England), May 29 2004, 328(7451) p1285.
9. Kumar N.B.; Cantor A; Allen K; Riccardi D; Besterman-Dahan K; Seigne J; Helal M; Salup R; Pow-Sang J. The specific role of isoflavones in reducing prostate cancer risk. Prostate (United States), May 1 2004, 59(2) p141-7.
10. Harkness LS; Fiedler K; Sehgal AR; Oravec D; Lerner E. Decreased bone resorption with soy isoflavone supplementation in postmenopausal women. J Womens Health (Larchmt) (United States), Nov 2004, 13(9) p1000-7.
11. Kritz-Silverstein D; Von Muhlen D; Barrett-Connor E; Bressel MA. Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study. Menopause (United States), May-Jun 2003, 10(3) p196-202.
12. Cheng SY; Shaw NS; Tsai KS; Chen CY. The hypoglycemic effects of soy isoflavones on postmenopausal women. J Womens Health (Larchmt) (United States), Dec 2004, 13(10) p1080-6.
13. Izumi T; Saito M; Obata A; Arii M; Yamaguchi H; Matsuyama A. Oral intake of soy isoflavone aglycone improves the aged skin of adult women. J Nutr Sci Vitaminol, Feb 2007, 53(1) p57-62.
14. Maron DJ; Lu GP; Cai NS; Wu ZG; LiYH; Chen H; Zhu JQ; Jin XJ; Wouters BC; Zhao J. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med, 2003, 163(12) p1448-53.
15. Hirano-Ohmori R; Takahashi R; Momiyama Y; Taniguchi H; Yonemura A; Tamai S; Umegaki K; Nakamura H; Kondo K; Ohsuzu F. Green tea consumption and serum malondialdehyde-modified LDL concentrations in healthy subjects. J Am Coll Nutr, Oct 2005, 24(5) p342-6.
16. Nagaya N; Yamamoto H; Uematsu M; Itoh T; Nakagawa K; Miyazawa T; Kangawa K; Miyatake K. Green tea reverses endothelial dysfunction in healthy smokers. Heart, 2004, 90(12) p1485-6.
17. Fujiki H; Suganuma M; Okabe S; Sueoka N; Komori A; Sueoka E; Kozu T; Tada Y; Suga K; Imai K; Nakachi K. Cancer inhibition by green tea. Mutat Res (Netherlands), Jun 18 1998, 402(1-2) p307-10.
18. Seely D; Mills EJ; Wu P; Verma S; Guyatt GH. The effects of green tea consumption on the incidence of breast cancer and recurrence of breast cancer: a systematic review and meta-analysis. Integr Cancer Ther, 2005, 4(2) p144-55.
19. Larsson SC; Wolk A. Tea consumption and ovarian cancer risk in a population-based cohort. Arch Intern Med (United States), Dec 12-26 2005, 165(22) p2683-6.
20. Schumacher B; Hoeijmakers JH; Garinis G.A. Sealing the gap between nuclear DNA damage and longevity. Mol Cell Endocrinol, 2009, 299(1) p112-7
21. Liu B; Wang J; Chan KM; Tjia W.M.; Deng W; Guan X; Huang JD; LiKM; Chau PY; Chen DJ; Pei D; Pendas AM; Cadinanos J; Lopez-Otin C; Tse HF; Hutchison C; Chen J; Cao Y; Cheah KS; Tryggvason K; Zhou Z. Genomic instability in laminopathy-based premature aging. Nat Med 2005, 11(7) p780-5.
22. Busuttil R; Bahar R; Vijg J. Genome dynamics and transcriptional deregulation in aging. Neuroscience, 2007, 145(4) p1341-7.
23. Gao YT; McLaughlin JK; Blot W.J.; Ji BT; Dai Q; Fraumeni JF. Reduced risk of esophageal cancer associated with green tea consumption. J Natl Cancer Inst, 1994, 86(11) p855-8.
24. Kurahashi N; Sasazuki S; Iwasaki M; Inoue M; Tsugane S. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol, 2008, 167(1) p71-7.
25. Kuriyama S; Hozawa A; Ohmori K; Shimazu T; Matsui T; Ebihara S; Avata S; Nagatomi R; Arai H; Tsuji I. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr, 2006, 83(2) p355-61.
26. ISO H; Date C; Wakai K; Fukui M; Tamakoshi A. The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med , 18 2006, 144(8) p554-62.
27. Muraki S; Yamamoto S; Ishibashi H; Oka H; Yoshimura N; Kawaguchi H; Nakamura K. Japanese elderly women at an osteoporosis outpatient clinic. J Orthop Sci, 2007, 12(4) p317-20.
28. Lee JH; Chung JH; Cho KH. The effects of epigallocatechin-3-gallate on extracellular matrix metabolism. J Dermatol Sci, 2005, 40(3) p195-204.
29. Marchioli R. Gli acidi grassi polinsaturi omega-3 e le malattie cardiovascolari. Minerva Cardioangiol, 2003, 51(5) p561-76.
30. Hong H; Xu ZM; Pang BS; Cui L; Wei Y; Guo W.J.; Mao YL; Yang XC. Effects of simvastain combined with omega-3 fatty acids on high sensitive C-reactive protein, lipidemia, and fibrinolysis in patients with mixed dyslipidemia. Chin Med Sci J, 2004, 19(2) p145-9.
31. Hamazaki K; Itomura M; Huan M; Nishizawa H; Sawazaki S; Tanouchi M; Watanabe S; Hamazaki T; Terasawa K; Yazawa K. Effect of omega-3 fatty acid-containing phospholipids on blood catecholamine concentrations in healthy volunteers: a randomized, placebo-controlled, double-blind trial. Nutrition, 2005, 21(6) p705-10.
32. Sirtori CR; Galli C. N-3 fatty acids and diabetes. Biomed Pharmacother, 2002, 56(8) p397-406.
33. San Giovanni JP; Chew EY. The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res, 2005, 24(1) p87-138.
34. Sublette ME; Hibbeln JR; Galfalvy H; Oquendo MA; Mann JJ. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry, 2006, 163(6) p1100-2.
35. Schlanger S; Shinitzky M; Yam D. Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia, 2002, 43(1) p103-4.
36. Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot Essent Fatty Acids, 2005, 73(5) p397-404.
37. Dunstan JA; Prescott SL. Does fish oil supplementation in pregnancy reduce the risk of allergic disease in infants. Curr Opin Allergy Clin Immunol , 2005, 5(3) p215-21.
38. Rahman K. Garlic and aging: new insights into an old remedy. Ageing Res Rev, 2003, 2(1) p39-56.
39. Ahmad MS; Ahmed N. Antiglycation properties of aged garlic extract: possible role in prevention of diabetic complications. J Nutr,2006, 136, p796S-799S.
40. Bhattacharya K; Yadava S; Papp T; Schiffmann D; Rahman Q. Reduction of chrysotile asbestos-induced genotoxicity in human peripheral blood lymphocytes by garlic extract. Toxicol Lett, 28 2004, 153(3) p327-32.
41. Borek C. Antioxidant health effects of aged garlic extract. J Nutr , Mar 2001, 131(3s) p1010S-5S.
42. Rahman K; Lowe GM. Garlic and cardiovascular disease: a critical review. J Nutr , 2006, 136(3 Suppl) p736S-740S.
43. Allison GL; Lowe GM; Rahman K. Aged garlic extract and its constituents inhibit platelet aggregation through multiple mechanisms. J Nutr,2006, 136(3 Suppl) p782S-788S.
44. Galeone C; Pelucchi C; Levi F; Negri E; Franceschi S; Talamini R; Giacosa A; La Vecchia C. Onion and garlic use and human cancer. Am J Clin Nutr, 2006, 84(5) p1027-32.
45. Fleischauer AT; Poole C; Arab L. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Am J Clin Nutr, 2000, 72(4) p1047-52.
46. Hsing AW; Chokkalingam AP; Gao YT; Madigan MP; Deng J; Gridley G; Fraumeni JF. Allium vegetables and risk of prostate cancer: a population-based study. J Natl Cancer Inst , 2002, 94(21) p1648-51.
47. Borek C. Garlic reduces dementia and heart-disease risk. J Nutr, 2006, 136(3 Suppl) p810S-812S.
48. Selvam R; Subramanian L; Gayathri R; Angayarkanni N. The anti-oxidant activity of turmeric (Curcuma longa). J Ethnopharmacol, 1995, 47(2) p59-67.
49. Thapliyal R; Deshpande SS; Maru GB. Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts. Cancer Lett , 2002, 175(1) p79-88.
50. Antero Salminen, Kai Kaarniranta. NF-κB Signaling in the Aging Process J Clin Immunol (2009) 29:397–405.
51. Aggarwal BB; Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol, 2008.
52. Lu X; Ji C; Xu H; LiX; Ding H; Ye M; Zhu Z; Ding D; Jiang X; Ding X; Guo X. Resveratrol-loaded polymeric micelles protect cells from Abeta-induced oxidative stress. Int J Pharm, Jun 22 2009, 375(1-2) p89-96.
53. Ishida T; Takeda T; Koga T; Yahata M; Ike A; Kuramoto C; Taketoh J; Hashiguchi I; Akamine A; Ishii Y; Yamada H. Attenuation of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity by resveratrol: a comparative study with different routes of administration. Biol Pharm Bull, May 2009, 32(5) p876-81.
54. Athar M; Back JH; Kopelovich L; Bickers DR; Kim AL. Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Arch Biochem Biophys, Jun 15 2009, 486(2) p95-102.
55. Bradamante S; Barenghi L; Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev, Fall 2004, 22(3) p169-88.
56. Karuppagonunder SS; Pinto JT; Xu H; Chen H.L.; Beal MF; Gibson G.E. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer's disease. Neurochem Int, Feb 2009, 54(2) p111-8.
57. Rivera L; Moron R; Zarzuelo A; Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol (England), Mar 15 2009, 77(6) p1053-63.
58. Philip Thomas, Jing Wu, Varinderpal Dhillon, Michael Fenech. Effect of dietary intervention on human micronucleus frequency in lymphocytes and buccal cells. Mutagenesis vol. 26 no. 1 pp. 69–76, 2011.
59. Qun Xu, Christine G Parks, Lisa A DeRoo, Richard M Cawthon, Dale P Sandler, and Honglei Chen. Multivitamin use and telomere length in women. Am J Clin Nutr 2009;89:1857-63.

First published: KOSMETIK international journal, No. 1 (47) / 2012