The senescence accelerated mouse prone 8 substrain (SAM-P8), widely accepted as an animal model for studying aging and antiaging drugs, was used to examine the effects of dietary supplementation with extracts of Cistanche deserticola (ECD) which has been used extensively in traditional Chinese medicine because of its perceived ability to promote immune function in the elderly. Eight-month-old male SAM-P8 mice were treated with ECD by daily oral administrations for 4 weeks. The results showed that dietary supplementation of 150？mg/kg and 450？mg/kg of ECD could extend the life span measured by Kaplan-Meier survival analysis in dose-dependent manner. Dietary supplementation of SAM-P8 mice for 4 weeks with 100, 500, and 2500？mg/kg of ECD was shown to result in significant increases in both naive T and natural killer cells in blood and spleen cell populations. In contrast, peripheral memory T cells and proinflammatory cytokine, IL-6 in serum, were substantially decreased in the mice that ingested 100 and 500？mg/kg of ECD daily. Additionally, Sca-1 positive cells, the recognized progenitors of peripheral naive T cells, were restored in parallel. Our results provide clear experimental support for long standing clinical observational studies showing that Cistanche deserticola possesses significant effects in extending life span and suggest this is achieved by antagonizing immunosenescence. 1. Introduction Cistanche deserticola, one of the most popular traditional Chinese herbal medicines/health products, has been described in a number of historical Chinese herbal pharmacopoeias as having antiaging properties. Consequently it has been widely used in China for treating various age-related disorders including senile dementia, impotence, infertility, chronic infection, and hematopoietic disorders in the elderly [1]. Modern chemical approaches have allowed two principal types of compounds, phenylethanoid glycosides and oligosaccharides, to be isolated as the main active ingredients of Cistanche deserticola [1]. In the last decade, Cistanche deserticola and its extracts have been studied intensively and shown to be capable of protecting neurons from injury induced by neurotoxins [2], inhibiting carbon tetrachloride induced hepatotoxicity [2], and promoting the recovery of bone marrow cells from Co60 induced radiation damage [3]. It has also been shown to have anti-inflammatory, antioxidant, and antiaging effects [4]. However, whether Cistanche deserticola can increase life span and what are the underlying molecular mechanisms [3] associated with its antiaging
References
[1]
Y. Jiang and P.-F. Tu, “Analysis of chemical constituents in Cistanche species,” Journal of Chromatography A, vol. 1216, no. 11, pp. 1970–1979, 2009.
[2]
Q. Xiong, K. Hase, Y. Tezuka, T. Tani, T. Namba, and S. Kadota, “Hepatoprotective activity of phenylethanoids from Cistanche deserticola,” Planta Medica, vol. 64, no. 2, pp. 120–125, 1998.
[3]
“Immunology and aging in Europe. Proceeding of the 2nd Conference on Basic Biology and Clinical Impact of Immunosenescence. March 22-26, 2001, Cordoba, Spain,” Experimental Gerontology, vol. 37, no. 2-3, pp. 183–473, 2002.
[4]
G.-D. Xuan and C.-Q. Liu, “Research on the effect of phenylethanoid glycosides (PEG) of the Cistanche deserticola on anti-aging in aged mice induced by D-galactose,” Journal of Chinese Medicinal Materials, vol. 31, no. 9, pp. 1385–1388, 2008.
[5]
D. Aw, A. B. Silva, and D. B. Palmer, “Immunosenescence: emerging challenges for an ageing population,” Immunology, vol. 120, no. 4, pp. 435–446, 2007.
[6]
M. Adibzadeh, H. Pohla, A. Rehbein, and G. Pawelec, “Long-term culture of monoclonal human T lymphocytes: models for immunosenescence?” Mechanisms of Ageing and Development, vol. 83, no. 3, pp. 171–183, 1995.
[7]
E. H. Greeley, E. Spitznagel, D. F. Lawler, R. D. Kealy, and M. Segre, “Modulation of canine immunosenescence by life-long caloric restriction,” Veterinary Immunology and Immunopathology, vol. 111, pp. 287–299, 2006.
[8]
S. N. Meydani, S. N. Han, and D. Wu, “Vitamin E and immune response in the aged: molecular mechanisms and clinical implications,” Immunological Reviews, vol. 205, pp. 269–284, 2005.
[9]
S. G. Deeks, “HIV infection, inflammation, immunosenescence, and aging,” Annual Review of Medicine, vol. 62, pp. 141–155, 2011.
[10]
M. Capri, D. Monti, S. Salvioli et al., “Complexity of anti-immunosenescence strategies in humans,” Artificial Organs, vol. 30, no. 10, pp. 730–742, 2006.
[11]
S. Antonaci, A. R. Garofalo, C. Chicco et al., “Senile dementia, Alzheimer type: a distinct entity in the immunosensescence?” Journal of Clinical Laboratory Analysis, vol. 4, no. 1, pp. 16–21, 1990.
[12]
R. Takahashi, “Anti-aging studies on the senescence accelerated mouse (SAM) strains,” Yakugaku Zasshi, vol. 130, no. 1, pp. 11–18, 2010.
[13]
S. Lloréns, R. M. M.-F. De Mera, A. Pascual et al., “The senescence-accelerated mouse (SAM-P8) as a model for the study of vascular functional alterations during aging,” Biogerontology, vol. 8, no. 6, pp. 663–672, 2007.
[14]
T. Takeda, “Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice,” Neurochemical Research, vol. 34, no. 4, pp. 639–659, 2009.
[15]
H. Nakahara, T. Kanno, Y. Inai et al., “Mitochondrial dysfunction in the senescence accelerated mouse (SAM),” Free Radical Biology and Medicine, vol. 24, no. 1, pp. 85–92, 1998.
[16]
J. Mizutani, T. Chiba, M. Tanaka, K. Higuchi, and M. Mori, “Unique mutations in mitochondrial DNA of senescence-accelerated mouse (SAM) strains,” Journal of Heredity, vol. 92, no. 4, pp. 352–355, 2001.
[17]
A. Mori, K. Utsumi, J. Liu, and M. Hosokawa, “Oxidative damage in the senescence-accelerated mouse,” Annals of the New York Academy of Sciences, vol. 854, pp. 239–250, 1998.
[18]
W. B. Ershler, W. H. Sun, N. Binkley et al., “Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction,” Lymphokine and Cytokine Research, vol. 12, no. 4, pp. 225–230, 1993.
[19]
A. N. Vallejo, “Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease,” Trends in Molecular Medicine, vol. 13, no. 3, pp. 94–102, 2007.
[20]
G. Pawelec, “Immunosenescence comes of age. Symposium on aging research in immunology: the impact of genomics,” EMBO Reports, vol. 8, no. 3, pp. 220–223, 2007.
[21]
M. L. Kohut and D. S. Senchina, “Reversing age-associated immunosenescence via exercise,” Exercise Immunology Review, vol. 10, pp. 6–41, 2004.
[22]
G. Pawelec, A. Akbar, C. Caruso, R. Effros, B. Grubeck-Loebenstein, and A. Wikby, “Is immunosenescence infectious?” Trends in Immunology, vol. 25, pp. 406–410, 2004.
[23]
G. Pawelec and C. Gouttefangeas, “T-cell dysregulation caused by chronic antigenic stress: the role of CMV in immunosenescence?” Aging, vol. 18, no. 2, pp. 171–173, 2006.
[24]
L. Ginaldi, M. De Martinis, D. Monti, and C. Franceschi, “Chronic antigenic load and apoptosis in immunosenescence,” Trends in Immunology, vol. 26, no. 2, pp. 79–84, 2005.
[25]
H. C. Hsu, D. K. Scott, and J. D. Mountz, “Impaired apoptosis and immune senescence—cause or effect?” Immunological Reviews, vol. 205, pp. 130–146, 2005.
[26]
S. Ferrando-Martínez, E. Ruiz-Mateos, A. Hernández et al., “Age-related deregulation of naive T cell homeostasis in elderly humans,” Age, vol. 33, no. 2, pp. 197–207, 2011.
[27]
C. Franceschi, M. Bonafè, S. Valensin, et al., “Inflamm-aging. An evolutionary perspective on immunosenescence,” Annals of the New York Academy of Sciences, vol. 908, pp. 244–254, 2000.
[28]
R. A. Daynes, B. A. Araneo, W. B. Ershler, C. Maloney, G.-Z. Li, and S.-Y. Ryu, “Altered regulation of IL-6 production with normal aging: possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative,” Journal of Immunology, vol. 150, no. 12, pp. 5219–5230, 1993.
[29]
M. Maggio, J. M. Guralnik, D. L. Longo, and L. Ferrucci, “Interleukin-6 in aging and chronic disease: a magnificent pathway,” The Journals of Gerontology A, vol. 61, pp. 575–584, 2006.
[30]
C. Caruso, D. Lio, L. Cavallone, and C. Franceschi, “Aging, longevity, inflammation, and cancer,” Annals of the New York Academy of Sciences, vol. 1028, pp. 1–13, 2004.
[31]
D. Di Bona, S. Vasto, C. Capurso et al., “Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis,” Ageing Research Reviews, vol. 8, no. 1, pp. 36–42, 2009.
[32]
R. Krishnaraj, “Immunosenescence of human NK cells: effects on tumor target recognition, lethal hit and interferon sensitivity,” Immunology Letters, vol. 34, no. 1, pp. 79–84, 1992.
