A Hypothetical Anti-Aging Mechanism of “Yang-Invigorating” Chinese Tonic Herbs

Abstract

Chinese tonic herbs are generally classified into Yin and Yang categories based on their health-promoting action. Emerging evidence has suggested that in addition to up-regulating mitochondrial functional status, Yang tonic herbs also enhance cellular/mitochondrial antioxidant capacity, and may thus prevent age-related diseases and prolong the healthy part of lifespan (i.e. healthspan). The proposed biochemical mechanism underlying the antioxidant action of Yang tonic herbs involves a sustained and low level of mitochondrial reactive oxygen species production, which is secondary to the increased activity of the electron transport chain, with the possible involvement of mitochondrial uncoupling. “Yang invigoration” improves antioxidant defense in the body in the long term and thereby offers a promising prospect for preventing or possibly delaying age-related diseases and the detrimental effects of aging.

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P. Lam, H. Wong, J. Chen and K. Ko, "A Hypothetical Anti-Aging Mechanism of “Yang-Invigorating” Chinese Tonic Herbs," Chinese Medicine, Vol. 3 No. 1, 2012, pp. 72-78. doi: 10.4236/cm.2012.31012.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] M. K. Shigenaga, T. M. Hagen and B. N. Ames, “Oxidative Damage and Mitochondrial Decay in Aging,” Proceedings of the National Academy of Sciences USA, Vol. 91, No. 23, 1994, pp. 10771-10778. doi:10.1073/pnas.91.23.10771
[2] B. N. Ames, M. K. Shigenaga and T. M. Hagen, “Oxidants, Antioxidants, and the Degenerative Diseases of Aging,” Proceedings of the National Academy of Sciences USA, Vol. 90, No. 17, 1993, pp. 7915-7922. doi:10.1073/pnas.90.17.7915
[3] D. Harman, “Aging: A Theory Based on Free Radical and Radiation Chemistry,” Journal of Gerontology, Vol. 11, No. 3, 1956, pp. 298-300.
[4] D. Harman, “The Biologic Clock: The Mitochondria?” Journal of the American Geriatrics Society, Vol. 20, No. 4, 1972, pp. 145-147.
[5] A. D. de Grey, “The Reductive Hotspot Hypothesis of Mammalian Aging: Membrane Metabolism Magnifies Mutant Mitochondrial Mischief,” European Journal of Biochemistry, Vol. 269, No. 8, 2002, pp. 2003-2009. doi:10.1046/j.1432-1033.2002.02868.x
[6] A. D. de Grey, “The Reductive Hotspot Hypothesis: An Update,” Archives of Biochemistry and Biophysics, Vol. 373, No. 1, 2000, pp. 295-301. doi:10.1006/abbi.1999.1509
[7] K. B. Beckman and B. N. Ames, “Mitochondrial Aging: Open Questions,” Annals of the New York Academy of Sciences, Vol. 854, 1998, pp. 118-127.
[8] K. B. Beckman and B. N. Ames, “The Free Radical Theory of Aging Matures,” Physiological Reviews, Vol. 78, No. 2, 1998, pp. 547-581.
[9] T. M. Hagen, D. L. Yowe, J. C. Bartholomew, C. M. Wehr, K. L. Do, J. Y. Park and B. N. Ames, “Mitochondrial Decay in Hepatocytes from Old Rats: Membrane Potential Declines, Heterogeneity and Oxidants Increase,” Proceedings of the National Academy of Sciences USA, Vol. 94, No. 7, 1997, pp. 3064-3069. doi:10.1073/pnas.94.7.3064
[10] N. Lane, “A Unifying View of Ageing and Disease: The Double-Agent Theory,” Journal of Theoretical Biology, Vol. 225, No. 4, 2003, pp. 531-540. doi:10.1016/S0022-5193(03)00304-7
[11] J. Lapointe and S. Hekimi, “When a Theory of Aging Ages Badly,” Cellular and Molecular Life Sciences, Vol. 67, No. 1, 2010, pp. 1-8. doi:10.1007/s00018-009-0138-8
[12] J. Wanagat, D. F. Dai and P. Rabinovitch, “Mitochondrial Oxidative Stress and Mammalian Healthspan,” Mechanisms of Ageing and Development, Vol. 131, No. 7-8, 2010, pp. 527-535. doi:10.1016/j.mad.2010.06.002
[13] M. Holzenberger, J. Dupont, B. Ducos, P. Leneuve, A. Geloen, P. C. Even, P. Cervera and Y. Le Bouc, “IGF-1 Receptor Regulates Lifespan and Resistance to Oxidative Stress in Mice,” Nature, Vol. 421, No. 6919, 2003, pp. 182-187. doi:10.1038/nature01298
[14] S. J. Lin, P. A. Defossez and L. Guarente, “Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces Cerevisiae,” Science, Vol. 289, No. 5487, 2000, pp. 2126-2128. doi:10.1126/science.289.5487.2126
[15] T. J. Schulz, K. Zarse, A. Voigt, N. Urban, M. Birringer and M. Ristow, “Glucose Restriction Extends Caenorhabditis Elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress,” Cell Metabolism, Vol. 6, No. 4, 2007, pp. 280-293. doi:10.1016/j.cmet.2007.08.011
[16] S. Wullschleger, R. Loewith and M. N. Hall, “TOR Signaling in Growth and Metabolism,” Cell, Vol. 124, No. 3, 2006, pp. 471-484. doi:10.1016/j.cell.2006.01.016
[17] R. M. Anderson, J. L. Barger, M. G. Edwards, K. H. Braun, C. E. O’Connor, T. A. Prolla and R. Weindruch, “Dynamic Regulation of PGC-1α Localization and Turnover Implicates Mitochondrial Adaptation in Calorie Restriction and the Stress Response,” Aging Cell, Vol. 7, No. 1, 2008, pp. 101-111. doi:10.1111/j.1474-9726.2007.00357.x
[18] L. A. Loeb, D. C. Wallace and G. M. Martin, “The Mitochondrial Theory of Aging and Its Relationship to Reactive Oxygen Species Damage and Somatic mtDNA Mutations,” Proceedings of the National Academy of Sciences USA, Vol. 102, No. 52, 2005, pp. 18769-18770. doi:10.1073/pnas.0509776102
[19] T. M. Hagen, J. Liu, J. Lykkesfeldt, C. M. Wehr, R. T. Ingersoll, V. Vinarsky, J. C. Bartholomew and B. N. Ames, “Feeding Acetyl-L-Carnitine and Lipoic Acid to Old Rats Significantly Improves Metabolic Function While Decreasing Oxidative Stress,” Proceedings of the National Academy of Sciences USA, Vol. 99, No. 4, 2002, pp. 1870-1875. doi:10.1073/pnas.261708898
[20] G. Paradies, F. M. Ruggiero, G. Petrosillo, M. N. Gadaleta and E. Quagliariello, “Effect of Aging and Acetyl-L-Carnitine on the Activity of Cytochrome Oxidase and Adenine Nucleotide Translocase in Rat Heart Mitochondria,” FEBS Letters, Vol. 350, No. 2-3, 1994, pp. 213-215. doi:10.1016/0014-5793(94)00763-2
[21] V. G. Desai, R. Weindruch, R. W. Hart and R. J. Feuers, “Influences of Age and Dietary Restriction on Gastrocnemius Electron Transport System Activities in Mice,” Archives of Biochemistry and Biophysics, Vol. 333, No. 1, 1996, pp. 145-151. doi:10.1006/abbi.1996.0375
[22] A. Navarro and A. Boveris, “Rat Brain and Liver Mitochondria Develop Oxidative Stress and Lose Enzymatic Activities on Aging,” American Journal of Physiology— Regulatory, Integrative and Comparative Physiology, Vol. 287, No. 5, 2004, pp. R1244-R1249. doi:10.1152/ajpregu.00226.2004
[23] R. J. Feuers, “The Effects of Dietary Restriction on Mitochondrial Dysfunction in Aging,” Annals of the New York Academy of Sciences, Vol. 854, 1998, pp. 192-201.
[24] S. Moghaddas, C. L. Hoppel and E. J. Lesnefsky, “Aging Defect at the QO Site of Complex III Augments Oxyradical Production in Rat Heart Interfibrillar Mitochondria,” Archives of Biochemistry and Biophysics, Vol. 414, No. 1, 2003, pp. 59-66. doi:10.1016/S0003-9861(03)00166-8
[25] J. Liu, E. Head, A. M. Gharib, W. Yuan, R. T. Ingersoll, T. M. Hagen, C. W. Cotman and B. N. Ames, “Memory Loss in Old Rats Is Associated with Brain Mitochondrial Decay and RNA/DNA Oxidation: Partial Reversal by Feeding Acetyl-L-Carnitine and/or R-α-Lipoic Acid,” Proceedings of the National Academy of Sciences USA, Vol. 99, No. 4, 2002, pp. 2356-2361. doi:10.1073/pnas.261709299
[26] J. Liu, D. W. Killilea and B. N. Ames, “Age-Associated Mitochondrial Oxidative Decay: Improvement of Carnitine Acetyltransferase Substrate-Binding Affinity and Activity in Brain by Feeding Old Rats Acetyl-L-Carnitine and/or R-α-Lipoic Acid,” Proceedings of the National Academy of Sciences USA, Vol. 99, No. 4, 2002, pp. 1876-1881. doi:10.1073/pnas.261709098
[27] J. Liu, H. Atamna, H. Kuratsune and B. N. Ames, “Delaying Brain Mitochondrial Decay and Aging with Mitochondrial Antioxidants and Metabolites,” Annals of the New York Academy of Sciences, Vol. 959, 2002, pp. 133-166.
[28] A. Ugidos, T. Nystrom and A. Caballero, “Perspectives on the Mitochondrial Etiology of Replicative Aging in Yeast,” Experimental Gerontology, Vol. 45, No. 7-8, 2010, pp. 512-515. doi:10.1016/j.exger.2010.02.002
[29] B. Halliwell, “Antioxidants in Human Health and Disease,” Annual Review of Nutrition, Vol. 16, 1996, pp. 33-50.
[30] K. M. Ko, T. Y. Leon, D. H. Mak, P. Y. Chiu, Y. Du and M. K. Poon, “A Characteristic Pharmacological Action of ‘Yang-Invigorating’ Chinese Tonifying Herbs: Enhancement of Myocardial ATP-Generation Capacity,” Phytomedicine, Vol. 13, No. 9-10, 2006, pp. 636-642. doi:10.1016/j.phymed.2006.02.007
[31] H. S. Wong, H. Y. Leung and K. M. Ko, “Yang-Invigorating Chinese Tonic Herbs Enhance Mitochondrial ATP Generation in H9c2 Cardiomyocytes,” Chinese Medicine, Vol. 2, No. 1, 2011, pp. 1-5.
[32] H. Y. Leung, P. Y. Chiu, M. K. Poon and K. M. Ko, “A Yang-Invigorating Chinese Herbal Formula Enhances Mitochondrial Functional Ability and Antioxidant Capacity in Various Tissues of Male and Female Rats,” Rejuvenation Research, Vol. 8, No. 4, 2005, pp. 238-247. doi:10.1089/rej.2005.8.238
[33] K. M. Ko and H. Y. Leung, “Enhancement of ATP Generation Capacity, Antioxidant Activity and Immunomodulatory Activities by Chinese Yang and Yin Tonifying Herbs,” Chinese Medicine, Vol. 2, 2007, p. 3.
[34] W. Liu, T. Ogata, S. Sato, K. Unoura and J. Onodera, “Superoxide Scavenging Activities of Sixty Chinese Medicines Determined by an ESR Spin-Trapping Method Using Electrogenerated Superoxide,” Yakugaku Zasshi, Vol. 121, No. 4, 2001, pp. 265-270. doi:10.1248/yakushi.121.265
[35] H. C. Liu, R. M. Chen, W. C. Jian and Y. L. Lin, “Cytotoxic and Antioxidant Effects of the Water Extract of the Traditional Chinese Herb Gusuibu (Drynaria fortunei) on Rat Osteoblasts,” Journal of the Formosan Medical Association, Vol. 100, No. 6, 2001, pp. 383-388.
[36] H. Haraguchi, J. Inoue, Y. Tamura and K. Mizutani, “Inhibition of Mitochondrial Lipid Peroxidation by Bakuchiol, a Meroterpene from Psoralea Corylifolia,” Planta Medica, Vol. 66, No. 6, 2000, pp. 569-571. doi:10.1055/s-2000-8605
[37] Y. T. Wong, K. K. Wong, K. Yeung and G. Mo, “Pharmacology and Clinical Research on Dipsacus Asperoides,” Pharmacology and Clinics of Chinese Materia Medica, Vol. 3, 1996, pp. 20-24.
[38] T. K. Yim and K. M. Ko, “Antioxidant and Immunodulatory Activities of Chinese Tonifying Herbs,” Pharmaceutical Biology, Vol. 40, No. 5, 2002, pp. 329-335. doi:10.1076/phbi.40.5.329.8457
[39] N. Chen and M. Ko, “Schisandrin B-Induced Glutathione Antioxidant Response and Cardioprotection Are Mediated by Reactive Oxidant Species Production in Rat Hearts,” Biological and Pharmaceutical Bulletin, Vol. 33, No. 5, 2010, pp. 825-829. doi:10.1248/bpb.33.825
[40] P. Y. Chiu, H. Y. Leung, A. H. Siu, N. Chen, M. K. Poon and K. M. Ko, “Long-Term Treatment with a Yang-Invigorating Chinese Herbal Formula Produces Generalized Tissue Protection against Oxidative Damage in Rats,” Rejuvenation Research, Vol. 11, No. 1, 2008, pp. 43-62. doi:10.1089/rej.2007.0577
[41] M. L. Chen, S. P. Ip, S. H. Tsai, K. M. Ko and C. T. Che, “Biochemical Mechanism of Wu-Zi-Yan-Zong-Wan, a Traditional Chinese Herbal Formula, against Alcohol-Induced Oxidative Damage in CYP2E1 cDNA-Transfected HepG2 (E47) Cells,” Journal of Ethnopharmacology, Vol. 128, No. 1, 2010, pp. 116-122. doi:10.1016/j.jep.2009.12.036
[42] M. L. Chen, S. H. Tsai, S. P. Ip, K. M. Ko and C. T. Che, “Long-Term Treatment with a 'Yang-Invigorating' Chinese Herbal Formula, Wu-Zi-Yan-Zong-Wan, Reduces Mortality and Liver Oxidative Damage in Chronic Alcohol-Intoxicated Rats,” Rejuvenation Research, Vol. 13, No. 4, 2010, pp. 459-467. doi:10.1089/rej.2009.0985
[43] Population Division of the Department of Economic and Social Affairs of the United Nation Secretariat, “World Population Ageing: 1950-2050,” New York, 2001.
[44] M. F. Beal, “Mitochondria Take Center Stage in Aging and Neurodegeneration,” Annals of Neurology, Vol. 58, No. 4, 2005, pp. 495-505. doi:10.1002/ana.20624
[45] D. C. Chan, “Mitochondria: Dynamic Organelles in Disease, Aging, and Development,” Cell, Vol. 125, No. 7, 2006, pp. 1241-1252. doi:10.1016/j.cell.2006.06.010
[46] T. T. Huang, E. J. Carlson, A. M. Gillespie, Y. Shi and C. J. Epstein, “Ubiquitous Overexpression of CuZn Superoxide Dismutase Does Not Extend Life Span in Mice,” Journal of Gerontology Series A: Biological Sciences and Medical Sciences, Vol. 55, No. 1, 2000, pp. B5-B9. doi:10.1093/gerona/55.1.B5
[47] R. J. Mockett, A. C. Bayne, L. K. Kwong, W. C. Orr and R. S. Sohal, “Ectopic Expression of Catalase in Drosophila Mitochondria Increases Stress Resistance But Not Longevity,” Free Radical Biology and Medicine, Vol. 34, No. 2, 2003, pp. 207-217. doi:10.1016/S0891-5849(02)01190-5
[48] W. C. Orr, R. J. Mockett, J. J. Benes and R. S. Sohal, “Effects of Overexpression of Copper-Zinc and Manganese Superoxide Dismutases, Catalase, and Thioredoxin Reductase Genes on Longevity in Drosophila Melanogaster,” Journal of Biological Chemistry, Vol. 278, No. 29, 2003, pp. 26418-26422. doi:10.1074/jbc.M303095200
[49] S. R. Steinhubl, “Why Have Antioxidants Failed in Clinical Trials?” American Journal of Cardiology, Vol. 101, No. 10A, 2008, pp. 14D-19D. doi:10.1016/j.amjcard.2008.02.003
[50] Y. Huang, “Gerontology,” Shanghai Science and Technology Press, Shanghai, 1989.
[51] G. H. Li, “The Differentiation and Treatment of Parkinson’s Disease According to Traditional Chinese Medicine,” Journal of Chinese Medicine, Vol. 30, 1989, pp. 1-4.
[52] X. Yu, Q. Meng, G. Zhao and B. Chen, “Clinical Management of Parkinson’s Disease by Chinese Medicine,” Proceedings of 4th National Conference on Integrated Chinese and Western Medicine on Health Promotion and Rehabililation Medicine, 2004, pp. 355-359.
[53] K. M. Ko, K. Chan, L. Shek, J. Yeung and S. H. Chui, “A ‘Yang-Invigorating’ Chinese Herbal Suppository Preparation Relieves Symptoms in Patients with Parkinson’s Disease,” New Trends in Alzheimer and Parkinson Related Disorders ADPD, 2005, pp. 243-246.
[54] K. M. Ko, P. Y. Chiu, H. Y. Leung, A. H. Siu, N. Chen, E. P. Leong and M. K. Poon, “Long-Term Dietary Supplementation with a Yang-Invigorating Chinese Herbal Formula Increases Lifespan and Mitigates Age-Associated Declines in Mitochondrial Antioxidant Status and Functional Ability of Various Tissues in Male and Female C57BL/6J Mice,” Rejuvenation Research, Vol. 13, No. 2-3, 2010, pp. 168-171. doi:10.1089/rej.2009.0893
[55] E. J. Anderson, H. Yamazaki and P. D. Neufer, “Induction of Endogenous Uncoupling Protein 3 Suppresses Mitochondrial Oxidant Emission during Fatty Acid-Supported Respiration,” Journal of Biological Chemistry, Vol. 282, No. 43, 2007, pp. 31257-31266. doi:10.1074/jbc.M706129200
[56] L. J. Toime and M. D. Brand, “Uncoupling Protein-3 Lowers Reactive Oxygen Species Production in Isolated Mitochondria,” Free Radical Biology and Medicine, Vol. 49, No. 4, 2010, pp. 606-611. doi:10.1016/j.freeradbiomed.2010.05.010
[57] G. Barja, “Aging in Vertebrates, and the Effect of Caloric Restriction: A Mitochondrial Free Radical Production-DNA Damage Mechanism?” Biological Reviews of the Cambridge Philosophical Society, Vol. 79, No. 2, 2004, pp. 235-251. doi:10.1017/S1464793103006213

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