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Print version ISSN 0365-0596
An. Bras. Dermatol. vol.85 no.1 Rio de Janeiro Jan./Feb. 2010
Milton Luiz GorzoniI; Sueli Luciano PiresII
IAdjunct Professor, Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil
IIProfessor, Instructor, Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil
The objective of antiaging medicine is to interfere in the normal human biological aging process. Is there any scientific basis to justify classifying antiaging medicine as a medical specialty and not a branch of basic biological science? This review evaluated 110 papers, nine of which (8.2% of the total) reported studies involving human subjects. Only one of these studies was randomized and double-blinded (Jadad 2). In accordance with their classification of recommendations and level of evidence, these studies were considered CII. Three of the nine articles were published in journals with an impact factor over 1.110. Therefore, there does not appear to be any solid scientific and/or clinical evidence that would justify the application of antiaging medicine in current medical practice.
Keywords: Aging; Clinical medicine; Evidence-based medicine
The basic principle of antiaging medicine, that of delaying, halting or reversing the normal human biological aging process, contradicts biogerontology, which distinguishes between aging as a natural phenomenon and the role of aging as a risk factor for certain diseases. The conduct of those who practice antiaging medicine should also be distinguished from public health-related actions for the promotion of health and disease prevention.
Organs and class associations, private and corporate medical plans and insurance companies in Brazil fail to recognize antiaging medicine as a medical specialty. Antiaging medicine focusses basically on the following areas:1
a) The reduction of oxidative stress through the use of dietary and/or mineral and/or vitamin supplements;
b) Calorie reduction and/or the use of pre- or probiotics;
c) Hormone replacement and/or supplementation;
d) Phytotherapeutic preparations;
e) Physical activity.
The basis and/or scientific evidence justifying its existence as a specialty of human medicine and not a branch of basic biological sciences are currently being questioned.
The objective of this review article was to use standardized, evidence-based scientific methodology to analyze studies published in journals in the field of human health that involve antiaging techniques, procedures and therapies, to attempt to define the level of evidence in these published studies, establish the percentage in which the methodological structure is sound and assess their applicability in current clinical practice.
To obtain the data for this paper, the following site was accessed on August 30, 2008 to search for relevant articles using the key words "antiaging medicine": http://www.nlm.nih.gov (Medline/PubMed). Articles consisting of reviews, editorials or discussions were excluded, as were descriptions of cosmetic or laboratory techniques and procedures and studies conducted in cells or animals. The studies found to have been conducted in samples of human populations were analyzed, preferably in their electronic versions and/or from their abstract on this site or on the site of the journal in which the paper was published. This analysis was based on the criteria described below:
a) In accordance with the score proposed by Jadad et al.2 that evaluates the probability of the occurrence of a study bias using seven items:
1. Was the study described as randomized or in similar terminology?
2. Was the study described as double-blinded?
3. Was withdrawal from previous drugs described?
4. Was an appropriate method for sequenced randomization described?
5. Was there a description of an appropriate double-blinding method?
6. Was the randomization method inappropriate?
7. Was the double-blinding method inappropriate?
Questions 1-5 are indicative of the quality of the study, one point being awarded for each positive answer and none in the case of negative answers. If the answers to questions 6 and 7 are affirmative, one point should be subtracted from the final score for each affirmative answer. Although this calculation does not evaluate all the elements of a study, it may be useful in making qualitative evaluations between weak (0) and strong (5 points).
b) In accordance with a summarized version of the classification of recommendations and levels of evidence defined in the Oxford Centre for Evidence-Based Medicine:3
Classification of recommendation
A: Good evidence supporting recommendation
B: Moderate evidence supporting recommendation
C: Poor evidence supporting or not supporting recommendation
Level of evidence
I - > 1 correctly controlled and randomized study.
II - > 1 clinical or case-control study or observations.
III - Clinical experience, descriptive studies or reports.
c) In accordance with the impact factor in the list of scientific journals in the Journal Citation Report - 2003 Science Edition.4
RESULTS OF THE REVIEW
The site: http://www.nlm.nih.gov (MedLine/PubMed) was accessed on August 30, 2008, using the key words "antiaging medicine" and 110 papers were identified 1,5-113, 103 of which were published entirely in English, while 7 were published in other languages (5 in Chinese, 1 in Japanese and 1 in German) with only their abstracts available in English. Their content was divided as follows:
a) Fifty-five papers (50.0% of the total) referred to reviews, editorials and discussions. 1,6,9,11-12,21,24,27,29,34,36,39-48,50-56,58,60-61,63,68,72-76,78-80,82,83,88,89,95-97,99,104,107,110,112 None of these papers consisted of systematic reviews, i.e. they were conducted in accordance with predefined criteria in an attempt to limit investigator bias. Systematic reviews frequently include meta-analyses of data from the studies evaluated in them; however, there were no cases of this type of paper.
b) One paper on the general principles of antiaging medicine 7 and five on cosmetic or laboratory techniques and procedures. 8,32-33,59,90
c) One paper could not be evaluated since not even its abstract was available electronically. Another paper was found to be unrelated to antiaging medicine.13
d) The remaining 47 papers referred principally to phytotherapeutic preparations and studies in cells, animals (ranging from insects to primates) and humans.
In this last category (human beings), 9 papers were found 14,17,25,28,30,64,67,86,109 (8.2% of the total). The principal characteristics of these papers are summarized in Table 1. Only one of these papers 109 describes the study as being randomized and double-blinded (Jadad 2), while another three 25,30,86 refer to a control group. Of a total of 8 clinical or observational studies 14,17,25,28,30,64,67,86, statistical analysis was adequately described in three papers.25,28,67
Each one of the nine papers dealt with different techniques, procedures and therapies, skin aging being the only factor in common linking four of these studies.14,28,30,67
The classification of recommendation of these nine papers 14,17,25,28,30,64,67,86,109 is considered "C" and the level of evidence "II".3
Only three of the journals in which these papers were published 28,30,109 had an impact factor over 1.110, placing them in the list of the 1,500 highest rated scientific journals according to this criterion. 114 On the other hand, two of the remaining journals had no impact factor whatsoever.25,86
COMMENTS ON THE REVIEW
Laboratory studies conducted in cells or in animals represent the first steps towards future studies and therapies in human beings. There are, however, significant distances between studies on the Drosophila melanogaster91 (fruit fly) or Musca domestica84,91 (housefly) and the immediate applicability of the findings in human beings. This would represent the most significant methodological error in antiaging medicine: inference, i.e. the extrapolation of results from basic science studies to medical practice without going through the clinical research stages.
Clinical research, also referred to as clinical trials or studies, is defined as a process of scientific investigation involving human beings. Basically, its purpose is to develop new drugs and procedures capable of having an effect on human health. Its execution requires compliance with steps defined in protocols elaborated for this purpose, based on national and international regulations. When related to the study of drugs, vaccines or diagnostic procedures, a study should be classified into one of four possible phases of clinical investigation. 115-118
a) Phase I: A drug used for the first time in normally healthy humans who generally do not have the disease for which the drug is being developed. The different routes of administration and the doses are evaluated and initial safety tests and tests to identify drug interactions are performed. Normally, the number of participants ranges from 20 to 100.
b) Phase II: Also known as a pilot study, this phase includes patients who have the disease for which the drug is being developed, the objective being to determine its safety and efficacy. Sample sizes range from 100 to 300 patients.
c) Phase III: After Phase II has been successfully concluded, the number of patients is increased in what are referred to as "amplified therapeutic or multicenter studies", in which the methodological structure is similar to that used in the previous phase. These are studies in which the duration of use is longer and the drug is compared with a placebo or with treatments that are already in use for the disease under evaluation. Their basic objective is to obtain further data, qualitatively or quantitatively, on the safety and efficacy of the drug and its interactions. If positive, the results of this phase contribute towards the registration and approval of the new drug for commercial use by the regulatory authorities. In this phase, studies evaluate between 300 and 3,000 patients.
d) Phase IV: Also known as post-marketing studies, these are conducted with the objective of evaluating the efficacy of the drug and detecting any side effects in populations using a drug that is now freely marketed to consumers who, in this phase, may number between thousands and millions.
With the exception of the study conducted by Predescu et al.109 in 343 elderly subjects, the other eight studies 14,17,25,28,30,64,67,86 reported samples ranging in size from 10 to 83 human participants, i.e. sample sizes compatible with Phase I clinical studies. Only two studies 28,64 used drugs in patients who had the disease; however, sample sizes were insufficient for the studies to be classified as Phase II. Likewise, the description of the study as being randomized or double-blind (Jadad 2) was only provided in the case of one study 109 and the use of a control group for comparative purposes was found in another three papers 25,30,86, thus raising doubts with respect to the scientific quality of these publications.
The absence of two studies coincidently dealing with the same therapy may be justified by the extent of the area of action proposed in antiaging medicine1; however, this failing also hampers the comparative analysis and duplication of the experiment, thus compromising the scientific value of findings. Even skin-aging, which was the subject of four of these papers,14,28,30,67 was evaluated using different methodologies and therapies, thereby hampering specific qualitative analysis.
The classification of recommendation "C" and level of evidence II reflect these methodological shortcomings. This also justifies the low impact factor of the majority of journals in which these papers were published.
Since the present literature review was able to identify only 9 papers referring to studies conducted exclusively in humans 14,17,25,28,30,64,67,86,109 and considering the vastness of the proposed field of action of antiaging medicine1, there is no solid scientific and/or clinical evidence that justifies its applicability in current medical practice.
1. Fisher A, Morley JE. Antiaging medicine: the good, the bad, and the ugly. J Gerontol A Biol Sci Med Sci. 2002;57:M636-9. [ Links ]
2. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1-12. [ Links ]
3. Phillips B, Ball C, Sackett D, Badenoch D, Straus S, Haynes B, et al. Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001). [acesso 1 Set 2008]. Disponível em: http://cebm.jr2.ox.ac.uk . [ Links ]
4. Journal Citation Report - 2003 Science Edition. [acesso 11 Set 2008]. Disponível em: http://www.research.hbi.ir/impact/Journal%20Citation%20Report%20%202003.htm. [ Links ]
5. Son BK, Akishita M. Vascular calcification and antiaging. Clin Calcium. 2008;18:912-7. [ Links ]
6. Chanchal D, Swarnlata S. Novel approaches in herbal cosmetics. J Cosmet Dermatol. 2008;7:89-95. [ Links ]
7. Rattan SI. Principles and practice of hormetic treatment of aging and age-related diseases. Hum Exp Toxicol. 2008;27:151-4. [ Links ]
8. Bruce S. Complementary effects of topical antiaging treatments in conjunction with aesthetic procedures. J Drugs Dermatol. 2008;7:s23-7. [ Links ]
9. Bruce S. Cosmeceuticals for the attenuation of extrinsic and intrinsic dermal aging. J Drugs Dermatol. 2008;7:s17-22. [ Links ]
10. Zhang Y, Dong XL, Leung PC, Che CT, Wong MS. Fructus ligustri lucidi extract improves calcium balance and modulates the calciotropic hormone level and vitamin D-dependent gene expression in aged ovariectomized rats. Menopause. 2008;15:558-65. [ Links ]
11. Enns LC, Wiley JC, Ladiges WC. Clinical relevance of transgenic mouse models for aging research. Crit Rev Eukaryot Gene Expr. 2008;18:81-91. [ Links ]
12. Marzetti E, Lawler JM, Hiona A, Manini T, Seo AY, Leeuwenburgh C. Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle. Free Radic Biol Med. 2008;44:160-8. [ Links ]
13. Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177:861-70. [ Links ]
14. Akhtar N, Yazan Y. Formulation and in-vivo evaluation of a cosmetic multiple emulsion containing vitamin C and wheat protein. Pak J Pharm Sci. 2008;21:45-50. [ Links ]
15. Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci USA. 2007;104:19796-801. [ Links ]
16. Talbourdet S, Sadick NS, Lazou K, Bonnet-Duquennoy M, Kurfurst R, Neveu M, et al. Modulation of gene expression as a new skin anti-aging strategy. J Drugs Dermatol 2007;6: S25-33. [ Links ]
17. Benito-Ruiz J, Raigosa JM, Manzano-Surroca M, Salvador L. Male chest enhancement: pectoral implants. Aesthetic Plast Surg. 2008;32:101-4. [ Links ]
18. Sultana N, Lee NH. Antielastase and free radical scavenging activities of compounds from the stems of Cornus kousa. Phytother Res. 2007;21:1171-6. [ Links ]
19. Luo D, Lin XF, Min W, Ma QH, Gu N, Jin SL, et al. Photoprotection by tocopherol submicron emulsion against UV-mediated damage in HaCaT cells. Methods Find Exp Clin Pharmacol. 2007;29:185-9. [ Links ]
20. Katsiki M, Chondrogianni N, Chinou I, Rivett AJ, Gonos ES. The olive constituent oleuropein exhibits proteasome stimulatory properties in vitro and confers life span extension of human embryonic fibroblasts. Rejuvenation Res. 2007;10:157-72. [ Links ]
21. Miller NL, Fulmer BR. Injection, ligation and transplantation: the search for the glandular fountain of youth. J Urol. 2007;177:2000-5. [ Links ]
22. Davis T, Wyllie FS, Rokicki MJ, Bagley MC, Kipling D. The role of cellular senescence in Werner syndrome: toward therapeutic intervention in human premature aging. Ann N Y Acad Sci. 2007;1100:455-69. [ Links ]
23. Briden E, Jacobsen E, Johnson C. Combining superficial glycolic acid (alpha-hydroxy acid) peels with microdermabrasion to maximize treatment results and patient satisfaction. Cutis. 2007;79:13-6. [ Links ]
24. Effron C, Briden ME, Green BA. Enhancing cosmetic outcomes by combining superficial glycolic acid (alpha-hydroxy acid) peels with nonablative lasers, intense pulsed light, and trichloroacetic acid peels. Cutis. 2007;79:4-8. [ Links ]
25. Shameem R, Latif SA. Healthy aged persons had a better adrenocortical function. Mymensingh Med J. 2007;16:61-3. [ Links ]
26. Haruna Y, Kashihara N, Satoh M, Tomita N, Namikoshi T, Sasaki T, et al. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci USA. 2007;104: 2331-6. [ Links ]
27. Kamel NS, Gammack J, Cepeda O, Flaherty JH. Antioxidants and hormones as antiaging therapies: high hopes, disappointing results. Cleve Clin J Med. 2006;73:1049-56,1058. [ Links ]
28. Metcalf S, Crowson AN, Naylor M, Haque R, Cornelison R. Imiquimod as an antiaging agent. J Am Acad Dermatol. 2007;56:422-5. [ Links ]
29. Kreyden OP. Antiaging - a scientific topic or just a social trend? J Cosmet Dermatol. 2005;4:228-9. [ Links ]
30. Fournier N, Fritz K, Mordon S. Use of nonthermal blue (405- to 420-nm) and near-infrared light (850- to 900nm) dual-wavelength system in combination with glycolic acid peels and topical vitamin C for skin photorejuvenation. Dermatol Surg. 2006;32:1140-6. [ Links ]
31. Kang SK, Kim KS, Kim SI, Chung KH, Lee IS, Kim CH. Immunosuppressive activity of deer antler extracts of Cervus korean TEMMINCK var. mantchuricus Swinhoe, on type II collagen-induced arthritis. In Vitro Cell Dev Biol Anim. 2006;42:100-7. [ Links ]
32. Arck PC, Overall R, Spatz K, Liezman C, Handjiski B, Klapp BF, et al. Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage. FASEB J. 2006;20:1567-9. [ Links ]
33. Fahy GM, Wowk B, Wu J. Cryopreservation of complex systems: the missing link in the regenerative medicine supply chain. Rejuvenation Res. 2006;9:279-91. [ Links ]
34. Calabrese V, Maines MD. Antiaging medicine: antioxidants and aging. Antioxid Redox Signal. 2006;8:362-4. [ Links ]
35. Zhang D, Zhang JJ. [Effect of Coeloglossum. viride var. bracteatum extract on oxidation injury in sub-acute senescent model mice]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2005; 27:729-33. [ Links ]
36. Micans P. The need for anti-aging medicine: the challenges faced to incorporate preventative medicine into the clinic and into society. Ann N Y Acad Sci. 2005;1057: 545-62. [ Links ]
37. Oktem G, Uslu S, Vatansever SH, Aktug H, Yurtseven ME, Uysal A. Evaluation of the relationship between inducible nitric oxide synthase (iNOS) activity and effects of melatonin in experimental osteoporosis in the rat. Surg Radiol Anat. 2006;28:157-62. [ Links ]
38. Assimopoulou NA, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res. 2005;19:997-1000. [ Links ]
39. Perls TT, Reisman NR, Olshansky SJ. Provision or distribution of growth hormone for "antiaging": clinical and legal issues. JAMA. 2005;294:2086-90. [ Links ]
40. Oxenkrug G. Antioxidant effects of N-acetylserotonin: possible mechanisms and clinical implications. Ann N Y Acad Sci. 2005;1053: 334-47. [ Links ]
41. Draelos ZD. Topical and oral estrogens revisited for antiaging purposes. Fertil Steril. 2005;84:291-2. [ Links ]
42. Hazzard WR. The conflict between biogerontology and antiaging medicine--do geriatricians have a dog in this fight? J Am Geriatr Soc. 2005;53:1434-5. [ Links ]
43. Whitehouse PJ, Juengst ET. Antiaging medicine and mild cognitive impairment: practice and policy issues for geriatrics. J Am Geriatr Soc. 2005;53:1417-22. [ Links ]
44. Grossman T. Latest advances in antiaging medicine. Keio J Med. 2005;54:85-94. [ Links ]
45. Farris PK. Topical vitamin C: a useful agent for treating photoaging and other dermatologic conditions. Dermatol Surg. 2005;31:814-7. [ Links ]
46. Cooper R, Morre DJ, Morre DM. Medicinal benefits of green tea: Part I. Review of noncancer health benefits. J Altern Complement Med. 2005;11:521-8. [ Links ]
47. Lee TK, Johnke RM, Allison RR, O'Brien KF, Dobbs LJ Jr. Radioprotective potential of ginseng. Mutagenesis. 2005;20:237-43. [ Links ]
48. Erol A. PPARalpha activators may be good candidates as antiaging agents. Med Hypotheses. 2005;65:35-8. [ Links ]
49. Assimopoulou AN, Papageorgiou VP. Radical scavenging activity of Alkanna tinctoria root extracts and their main constituents, hydroxynaphtho quinones. Phytother Res. 2005;19: 141-7. [ Links ]
50. Matsakas A, Diel P. The growth factor myostatin, a key regulator in skeletal muscle growth and homeostasis. Int J Sports Med. 2005;6:83-9. [ Links ]
51. Stock GB. The pitfalls of planning for demographic change. Ann N Y Acad Sci. 2004;1019:546-51. [ Links ]
52. Riga D, Riga S, Schneider F. Regenerative medicine: Antagonic-Stress therapy in distress and aging. I. Preclinical synthesis--2003. Ann N Y Acad Sci. 2004;1019:396-400. [ Links ]
53. Ukraintseva SV, Arbeev KG, Michalsky AI, Yashin AI. Antiaging treatments have been legally prescribed for approximately thirty years. Ann N Y Acad Sci. 2004;1019:64-9. [ Links ]
54. Fisher AL, Hill R. Ethical and legal issues in antiaging medicine. Clin Geriatr Med. 2004;20:361-82. [ Links ]
55. Banks WA, Farr SA. Antiaging methods and medicines for the memory. Clin Geriatr Med. 2004;20:317-28. [ Links ]
56. Hajjar RR. Cancer in the elderly: is it preventable? Clin Geriatr Med. 2004;20:293-316. [ Links ]
57. Brown-Borg HM. Antiaging supplement holds promise to halt age-related cognitive deterioration. Exp Biol Med (Maywood). 2004;229:367-8. [ Links ]
58. Navarro A. Mitochondrial enzyme activities as biochemical markers of aging Mol Aspects Med. 2004;25:37-48. [ Links ]
59. Briden ME. Alpha-hydroxyacid chemical peeling agents: case studies and rationale for safe and effective use. Cutis. 2004;73:18-24. [ Links ]
60. Carrillo-Vico A, Calvo JR, Abreu P, Lardone PJ, Garcia-Maurino S, Reiter RJ, et al. Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance. FASEB J. 2004;18:537-9. [ Links ]
61. Lomnitski L, Bergman M, Nyska A, Ben Shaul V, Grossman S. Composition, efficacy, and safety of spinach extracts. Nutr Cancer. 2003;46:222-31. [ Links ]
62. Juliet PA, Balasubramaniam D, Balasubramaniam N, Panneerselvam C. Carnitine: a neuromodulator in aged rats. J Gerontol A Biol Sci Med Sci. 2003;58:970-4. [ Links ]
63. Aburjai T, Natsheh FM. Plants used in cosmetics. Phytother Res. 2003;17:987-1000. [ Links ]
64. Yang CC, Chen JC, Chen GW, Chen YS, Chung JG. Effects of Shao-Fu-Zhu-Yu-Tang on motility of human sperm. Am J Chin Med. 2003;31:573-9. [ Links ]
65. Russo A, Izzo AA, Borrelli F, Renis M, Vanella A. Free radical scavenging capacity and protective effect of Bacopa monniera L. on DNA damage. Phytother Res. 2003;17:870-5. [ Links ]
66. Bergamini E. In response to: "Is there an antiaging medicine?" J Gerontol A Biol Sci Med Sci. 2003;58:483. [ Links ]
67. Bauza E, Dal Farra C, Berghi A, Oberto G, Peyronel D, Domloge N. Date palm kernel extract exhibits antiaging properties and significantly reduces skin wrinkles. Int J Tissue React. 2002;24:131-6. [ Links ]
68. Juengst ET, Binstock RH, Mehlman MJ, Post SG. Aging. Antiaging research and the need for public dialogue. Science. 2003;299:1323. [ Links ]
69. Xing H, Hu X, Liu H, Li Y, Chen Y. [Study on DNA oxidative damage of O3 aging model in mice]. Hua Xi Yi Ke Da Xue Xue Bao. 2001;32:229-31. [ Links ]
70. Li K, Liu M, Wei X. Study of xixin, duzhong and mixture to the antioxidant system of D-galactose -induced senile mice. Zhong Yao Cai 2000;23:161-3. [ Links ]
71. Shimokawa I, Fukuyama T, Yanagihara-Outa K, Tomita M, Komatsu T, Higami Y, et al. Effects of caloric restriction on gene expression in the arcuate nucleus. Neurobiol Aging 2003;24:117-23. [ Links ]
72. Altwein JE, Keuler FU. [Prevention and complementary medicine in aging]. Urologe A. 2002;41:318-24. [ Links ]
73. Butler RN, Fossel M, Harman SM, Heward CB, Olshansky SJ, Perls TT, et al. Is there an antiaging medicine? J Gerontol A Biol Sci Med Sci. 2002;57:B333-8. [ Links ]
74. Olshansky SJ, Hayflick L, Carnes BA. Position statement on human aging. J Gerontol A Biol Sci Med Sci. 2002;57:B292-7. [ Links ]
75. Schneider RH, Alexander CN, Salerno JW, Robinson DK Jr, Fields JZ, Nidich SI. Disease prevention and health promotion in the aging with a traditional system of natural medicine: Maharishi Vedic Medicine. J Aging Health. 2002;14:57-78. [ Links ]
76. Roth GS, Ingram DK, Lane MA. Caloric restriction in primates and relevance to humans. Ann N Y Acad Sci. 2001;928:305-15. [ Links ]
77. Shin KH, Lim SS, Lee SH, Lee YS, Cho SY. Antioxidant and immunostimulating activities of the fruiting bodies of Paecilomyces japonica, a new type of Cordyceps sp. Ann N Y Acad Sci. 2001;928: 261-73. [ Links ]
78. Knoll J. Antiaging compounds: (-)deprenyl (selegeline) and (-)1-(benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective highly potent enhancer of the impulse propagation mediated release of catecholamine and serotonin in the brain. CNS Drug Rev. 2001;7:317-45. [ Links ]
79. Bartke A, Coschigano K, Kopchick J, Chandrashekar V, Mattison J, Kinney B, et al. Genes that prolong life: relationships of growth hormone and growth to aging and life span. J Gerontol A Biol Sci Med Sci. 2001;56:B340-9. [ Links ]
80. Vojta CL, Fraga PD, Forciea MA, Lavizzo-Mourey R. Antiaging therapy: an overview. Hosp Pract (Minneap). 2001;36:43-9. [ Links ]
81. Russo A, Izzo AA, Cardile V, Borrelli F, Vanella A. Indian medicinal plants as antiradicals and DNA cleavage protectors. Phytomedicine. 2001;8:125-32. [ Links ]
82. Borek C. Antioxidant health effects of aged garlic extract. J Nutr. 2001;131:1010S-5S. [ Links ]
83. Farris PK. Office dispensing: a responsible approach. Semin Cutan Med Surg. 2000;19: 195-200. [ Links ]
84. Cui X, Dai XG, Li WB, Zhang BL, Fang YZ. Effects of Lu-Duo-Wei capsules on superoxide dismutase activity and contents of malondialdehyde and lipofuscin in the brain of the housefly. Am J Chin Med. 2000;28:259-62. [ Links ]
85. Calabrese V, Scapagnini G, Catalano C, Dinotta F, Geraci D, Morganti P. Biochemical studies of a natural antioxidant isolated from rosemary and its application in cosmetic dermatology. Int J Tissue React. 2000;22:5-13. [ Links ]
86. Liu J, Wang S, Liu H, Zhang C, Yang L, Zhang J. The immunomarker of aging and the modulatory effect of Chinese medicinal herbs on the dysfunction of lymphocytes in the elderly. J Environ Pathol Toxicol Oncol. 2000;19:153-8. [ Links ]
87. Shimokawa I, Yanagihara K, Higami Y, Okimoto T, Tomita M, Ikeda T, et al. Effects of aging and dietary restriction on mRNA levels of receptors for growth hormone-releasing hormone and somatostatin in the rat pituitary. J Gerontol A Biol Sci Med Sci. 2000;55:B274-9. [ Links ]
88. Vazquez B, Ortiz C, San Roman J, Plasencia MA, Lopez-Bravo A. Hydrophilic polymers derived from vitamin E. J Biomater Appl. 2000;14:367-88. [ Links ]
89. Shimokawa I, Higami Y. A role for leptin in the antiaging action of dietary restriction: a hypothesis. Aging (Milano). 1999;11:380-2. [ Links ]
90. Calabrese V, Scapagnini G, Randazzo SD, Randazzo G, Catalano C, Geraci G, et al. Oxidative stress and antioxidants at skin biosurface: a novel antioxidant from lemon oil capable of inhibiting oxidative damage to the skin. Drugs Exp Clin Res. 1999;25:281-7. [ Links ]
91. Cui X, Dai XG, Li WB, Zhang BL, Fang YZ. Effects of luduo-wei capsule on prolonging life span of housefly and Drosophila melanogaster. Am J Chin Med. 1999;27: 407-13. [ Links ]
92. Calabrese V, Randazzo SD, Catalano C, Rizza V. Biochemical studies on a novel antioxidant from lemon oil and its biotechnological application in cosmetic dermatology. Drugs Exp Clin Res .1999;25:219-25. [ Links ]
93. Boisnic S, Branchet-Gumila MC, Le Charpentier Y, Segard C. Repair of UVA-induced elastic fiber and collagen damage by 0.05% retinaldehyde cream in an ex vivo human skin model. Dermatology. 1999;199Suppl1:43-8. [ Links ]
94. Calabrese V, Randazzo SD, Morganti PG, Rizza V. An ex vivo biochemical model to study the antioxidant clinical properties of cosmetic products in human antiaging skin care. Drugs Exp Clin Res. 1999;25:43-9. [ Links ]
95. Manyam BV. Dementia in Ayurveda. J Altern Complement Med. 1999;5:81-8. [ Links ]
96. Misra R. Modern drug development from traditional medicinal plants using radioligand receptor-binding assays. Med Res Rev. 1998;18:383-402. [ Links ]
97. Khalsa DS. Integrated medicine and the prevention and reversal of memory loss. Altern Ther Health Med. 1998;4:38-43. [ Links ]
98. Novelli M, Masiello P, Bombara M, Bergamini E. Protein glycation in the aging male Sprague-Dawley rat: effects of antiaging diet restrictions. J Gerontol A Biol Sci Med Sci. 1998;53:B94-101. [ Links ]
99. Ma YX, Yue Z, Wang ZS, Chen SQ, Liang ZJ, Zhang JG, et al. Physiological basis for long life span. Mech Ageing Dev. 1997;98:47-55. [ Links ]
100. Ma YX, Zhu Y, Wang CF, Wang ZS, Chen SY, Shen MH, et al. The aging retarding effect of 'Long-Life CiLi'. Mech Ageing Dev. 1997;96:171-80. [ Links ]
101. Li JQ, Li ZK, Duan H, Zhang JT. [Effect of age and gin senoside Rg1 on nitric oxide content and nitric oxide synthase activity of cerebral cortex in rats]. Yao Xue Xue Bao. 1997; 32:251-4. [ Links ]
102. Li JQ, Zhang JT. [Effects of age and ginsenoside RG1 on membrane fluidity of cortical cells in rats]. Yao Xue Xue Bao. 1997;32:23-7. [ Links ]
103. Nishiyama N, Moriguchi T, Saito H. Beneficial effects of aged garlic extract on learning and memory impairment in the senescence-accelerated mouse. Exp Gerontol. 1997;32:149-60. [ Links ]
104. Isoyama S. Age-related changes before and after imposition of hemodynamic stress in the mammalian heart. Life Sci. 1996;58:1601-14. [ Links ]
105. Zhao Y, Wang X, Kawai M, Liu J, Liu M, Mori A. Antioxidant activity of Chinese ant extract preparations. Acta Med Okayama 1995;49:275-9. [ Links ]
106. Liu M, Zhang J. Effects of ginsenoside Rb1 and Rg1 on synaptosomal free calcium level, ATPase and calmodulin in rat hippocampus. Chin Med J (Engl). 1995;108:544-7. [ Links ]
107. Nose Y. 5th WAA Congress therapeutic artificial organs, 10 years after. Artif Organs 1995;19:204-10. [ Links ]
108. Ortmeyer HK, Bodkin NL, Hansen BC. Chronic calorie restriction alters glycogen metabolism in rhesus mon keys. Obes Res. 1994;2:549-55. [ Links ]
109. Predescu V, Riga D, Riga S, Turlea J, Barbat IM, Botezat-Antonescu L. Antagonic-stress. A new treatment in gerontopsychiatry and for a healthy productive life. Ann N Y Acad Sci. 1994;717:315-31. [ Links ]
110. Randerath K, Li D, Nath R, Randerath E. Exogenous and endogenous DNA modifications as monitored by 32P-postlabeling: relationships to cancer and aging. Exp Gerontol. 1992;27:533-49. [ Links ]
111. Chung MH, Kasai H, Nishimura S, Yu BP. Protection of DNA damage by dietary restriction. Free Radic Biol Med. 1992;12:523-5. [ Links ]
112. Regelson W, Franson R. Phospholipase A2 as a "death trigger" in the aging process. The use of PLA2 inhibitors as antiaging substances. Ann N Y Acad Sci. 1991;621:262-76. [ Links ]
113. Liu J, Edamatsu R, Kabuto H, Mori A. Antioxidant action of guilingji in the brain of rats with FeCl3-induced epilepsy. Free Radic Biol Med. 1990;9:451-4. [ Links ]
116. Brasil - Ministério da Saúde - Conselho Nacional de Saúde. Resolução 196/96 - Diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. [acesso 13 Set 2008]. Disponível em: http://conselho.saude.gov.br/comissao/conep/resolucao.html. [ Links ]
117. Brasil - Ministério da Saúde - Conselho Nacional de Saúde. Resolução 251/97 - Normas de pesquisa com novos fármacos, medicamentos, vacinas e testes diagnósticos envolvendo seres humanos. [acesso 13 Set 2008]. Disponível em: http://conselho.saude.gov.br/comissao/conep/resolucao.html . [ Links ]
118. Brasil - Ministério da Saúde - Agência Nacional de Vigilância Sanitária. Resolução RDC nº39 sobre regulamento para a realização de pesquisa clínica. [acesso 13 Set 2008]. Disponível em: http://e-legis.anvisa.gov.br/leisref/public/showAct.php?id=31279 . [ Links ]
Mailing Address: Aprovado pelo Conselho Editorial e aceito para publicação em 17.04.2009. * The study was developed at the Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil.
Milton Luiz Gorzoni
Hospital Geriátrico e de Convalescentes Dom Pedro II
Avenida Guapira, 2674
02265 002 São Paulo SP
Tel.:/Fax: 11 2176 1204 / 5589-9408
Conflict of interest: None
The present study was part of Project No. 371/08, approved by the Internal Review Board of the Sisterhood of the Santa Casa de Misericórdia, São Paulo, SP, Brazil.
Aprovado pelo Conselho Editorial e aceito para publicação em 17.04.2009.
* The study was developed at the Dom Pedro II Geriatric and Convalescent Hospital and the Basic Gerontology Course of the Department of Clinical Medicine, School of Medical Sciences, Santa Casa de São Paulo, São Paulo, SP, Brazil.