Restore Youthful Immune Function

The diseases of aging such as cancer, pneumonia, and dementia are linked to a malfunctioning immune system.

This degenerative impairment is known as immune senescence. It accelerates aging by causing chronic inflammation while failing to protect against pathogens and malignancies.^1-5

Not only do we lose the ability to defend against cancers and infections, but our failing immune cells create a state of hyper-inflammation that destroys neurons, the endothelium, and joints.^6,7

In an effort to reverse this decline, Life Extension® is interacting with scientists seeking to restore youthful immune function. Each advance we uncover urgently needs to transition into routine clinical practice.

Researchers have identified three natural compounds that have been shown to reverse a broad spectrum of harmful changes that occur in the immune system with advancing age.

These three compounds are extracts of Reishi mushrooms, Cistanche and Pu-erh tea.

Each of these natural compounds produces unique immune system-modulating effects that deter the pathologic components of immune senescence.

Together, these nutrients can help improve immune functions lost to aging.

Rejuvenate the Immune System

If we are to live longer, healthier lives, we need our immune system to function at peak capacity.

Three compounds that have demonstrated an impressive ability to rescue the immune system from senescent decline are:

1) Cistanche

2) Reishi mushrooms

3) Pu-erh tea

Together, these natural extracts help combat immune senescence by several complementary mechanisms that include enhancing activity of natural killer cells and T cells.

Reishi Mushroom Extract

Reishi Mushrooms

The immune-boosting properties of Reishi mushrooms have been appreciated in Eastern medicine for thousands of years. Modern science is just now beginning to validate their health-promoting properties.^8,9

Studies show that consuming these mushrooms improves immune function and has anti-tumor effects.^9-16 In mice, Reishi has been found to promote the maturation and activation of immune system cells such as T cells, natural killer cells, dendritic cells, and macrophages.^10-13 Lab studies show that Reishi also helps raise protective IL-10 levels and lower pro-inflammatory IL-6 levels.^17,18

This indicates that Reishi augments the function of both the innate and adaptive immune system.

The innate immune system can be thought of as the body's first line of defense, responding rapidly to potentially harmful insults such as viruses, bacteria, and cancer cells.

Natural killer cells are an important component of this innate immunity.^19-24 The diminished numbers of active natural killer cells that can occur with aging predispose an individual to high rates of infection by viruses ranging from the common cold to herpes viruses.^23-28

The adaptive immune system acts slower than the innate immune system but mounts a more specific, powerful attack against pathogens using specialized immune system cells called T cells.

With its ability to boost components of both innate and adaptive immunity, Reishi can protect the aging body from infections. This benefit has been borne out in laboratory studies demonstrating protection from many common viruses, including:

• Herpes simplex viruses—which cause oral and genital herpes viruses²⁹
• Influenza viruses—which cause the flu³⁰
• Epstein-Barr virus—which causes mononucleosis but can also contribute to the formation of cancer^31,32
• Hepatitis B virus—a common cause of liver disease that can lead to liver failure^33,34
• Human immunodeficiency virus (HIV)—the virus which causes AIDS^35,36

In addition to offering protection from infection, Reishi exhibits anti-cancer properties as well—largely because of its ability to enhance immune function. In particular, the boost Reishi gives to natural killer cell, T cell, and macrophage function aids in the identification and destruction of abnormal cells that may develop into cancer.^9,16

Reishi can also directly combat tumors by impairing the ability of tumor cells to grow, preventing tumor blood vessels from developing, starving the abnormal cells, and even directly killing cancer cells.^9,16

In one study, Reishi mushrooms were applied to various human cancer cell lines.¹⁶ Not only did the Reishi reduce the growth of the cells, but it induced cell death in many of the diseased cells.

Perhaps most impressively, Reishi has been shown to significantly extend lifespan of mice.³⁷ Researchers followed two groups of mice, one fed a normal control diet and the other fed a diet enriched with a Reishi extract. When most of the mice had passed away from old age, the Reishi supplemented group had lived as much as 148 days longer than the control group. Given that the lifespan of a mouse is typically less than two years, this represents a dramatic increase in longevity.

These studies provide support for why Reishi has earned the nickname, “mushroom of immortality.”

Cistanche Extract

Cistanche

Cistanche is a type of desert plant that, like Reishi mushrooms, has long been appreciated for its medicinal uses in Eastern medicine. Recently, several studies have confirmed the ability of Cistanche extract to boost immune cells in the body.^38-41

In one study, researchers utilized a strain of senescence-accelerated mice, which age more rapidly than normal mice and display the same deterioration in immune function seen in human immune senescence. The mice fed a diet supplemented with Cistanche extract for only four weeks were found to have a significantly increased number of both T cells and natural killer cells in the blood, while lowering pro-inflammatory IL-6 levels in blood.

This enhancement in immune function translated to an extended lifespan as well. The average age after supplementation with Cistanche was 15% longer than controls.³⁸

In addition to T cells and natural killer cells, Cistanche also helps activate other important immune cells, including macrophages, dendritic cells, and B cells.^39,40

Encouraging results have been demonstrated in a human study as well. When elderly subjects took 100 mg of Cistanche extract daily for 12 weeks, there was a 6.1% increase in helper T cells and an almost 12% increase in natural killer cell activity. This increase represents a significant immune-boosting effect.⁴¹

Patients also experienced improved markers of vascular function and a decrease in fatigue. No significant adverse effects were observed.

Given that these same improvements in immune function resulted in enhanced longevity in animal studies, it can be assumed that the rejuvenating effect Cistanche has on the human immune system may assist in prolonging human lifespan as well.

Pu-erh Tea Extract

Pu-erh Tea

Both green tea and black tea have long been cherished for their numerous health benefits. One particular variety of fermented black tea, called Pu-erh, is especially beneficial for the aging immune system.⁴²

Studies show that Pu-erh tea and its extract combat immune senescence by multiple mechanisms.⁴² Two of the chief ones include increasing natural killer and T cells.

In addition to its ability to bolster the immune system itself, Pu-erh tea appears to provide even more protection from infection with direct antibacterial and antiviral effects as well. Several studies have demonstrated that Pu-erh tea directly kills or inhibits the growth of bacteria and suppresses the growth of viruses such as hepatitis B virus.⁴²

It also displays anti-tumor effects and it has been shown to lower cholesterol levels, fight obesity, and help control diabetes.⁴²

In one investigation, scientists studied the effects of Pu-erh tea on the senescence-accelerated strain of mice discussed previously.⁴³

Before supplementation with Pu-erh tea, the mice demonstrated the same features of immune system deterioration seen in aging humans, including lower numbers of active T cells and natural killer cells. In addition, levels of the powerful pro-inflammatory cytokine IL-6 were markedly elevated in the senescence-accelerated mice, compared with controls. Remarkably, treating these mice with Pu-erh tea reversed their immune senescence.

The treated mice experienced enhanced numbers of T cells and natural killer cells and a significant 43% decrease in IL-6—benefits that more closely resemble a normal healthy immune system.

Based on these immune-boosting results, the researchers concluded that intake of Pu-erh tea may help older individuals prevent infection and cancer.

Powerful Anti-Inflammatory Effects in Humans

A human study of Pu-erh tea extract further emphasizes its role in reversing inflammatory cytokine levels. The study was performed among a group of patients with metabolic syndrome, a common condition defined by central obesity, borderline or high fasting glucose, and elevated triglycerides and cholesterol.⁴⁴ Those with metabolic syndrome have higher levels of inflammation and are at an increased risk of having immune impairments.⁴⁵

Subjects were given either Pu-erh tea extract twice daily or a placebo. They were instructed to exercise and observe a healthy diet during the study period, but were permitted no medicines that might otherwise affect the results.

After three months, patients provided blood samples for analysis of inflammatory cytokines and other markers of inflammation.

As expected, placebo recipients showed no significant changes in blood levels of TNF-a or IL-6 (pro-inflammatory cytokine), IL-10 (an anti-inflammatory cytokine), or C-reactive protein (CRP, a marker of total body inflammation).

Subjects supplemented with Pu-erh tea extract showed robust improvements in immune status, including:

• 21% reduction in IL-6,
• 23% reduction in TNF-a,
• 26% reduction in CRP, indicating significant decreases in their overall inflammatory status, and
• 34% increase of inflammation-quelling IL-10, further demonstrating the overall reduction in inflammation.

Clearly, Pu-erh tea extract offers multiple benefits to prevent the progress of immune senescence. But, just as a good roof provides multiple, overlapping structures to prevent leaks, good immune system coverage should offer multiple, overlapping mechanisms to ensure that no possible holes are left to allow untimely infections, inflammation, or cancers to progress.

Summary

 

Immune senescence puts the elderly at increased risk for frequent and severe infections, cancer, and a variety of chronic inflammatory diseases.

Compounds found in various plants and fungi bolster the weakened immune system, improving immunity and reducing the risk for infections and cancer.

Reishi mushrooms, Cistanche, and Pu-erh tea boost the immune system by several complementary mechanisms, including amplifying the activity of natural killer cells, T cells, and various other immune system components.

Adding these immune-boosters to the diet may help thwart waning immunity in older age, helping give our body a fighting chance against many infectious diseases and cancer.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

1. Ginaldi L, De Martinis M, D'Ostilio A, et al. The immune system in the elderly: I. Specific humoral immunity. Immunol Res. 1999;20(2):101-8.
2. Ginaldi L, De Martinis M, D'Ostilio A, et al. The immune system in the elderly: II. Specific cellular immunity. Immunol Res. 1999;20(2):109-15.
3. Ginaldi L, De Martinis M, D'Ostilio A, et al. The immune system in the elderly: III. Innate immunity. Immunol Res. 1999;20(2):117-26.
4. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol. 2007 Jan;211(2):144-56.
5. Pawelec G. Hallmarks of human “immunosenescence”: adaptation or dysregulation? Immun Ageing. 2012 Jul 25;9(1):15.
6. Bueno V, Sant'Anna OA, Lord JM. Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease. Age (Dordr). 2014;36(6):9729.
7. Pera A, Campos C, Lopez N, et al. Immunosenescence: Implications for response to infection and vaccination in older people. Maturitas. 2015 Sep;82(1):50-5.
8. Babu PD, Subhasree R. The sacred mushroom “Reishi”-a review. American-Eurasian Journal of Botany. 2008;1(3):107-10.
9. Xu Z, Chen X, Zhong Z, et al. Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities. Am J Chin Med. 2011;39(1):15-27.
10. Cao LZ, Lin ZB. Regulation on maturation and function of dendritic cells by Ganoderma lucidum polysaccharides. Immunol Lett. 2002 Oct 1;83(3):163-9.
11. Chang CJ, Chen YY, Lu CC, et al. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin. Innate Immun. 2014 Apr;20(3):301-11.
12. Wang PY, Zhu XL, Lin ZB. Antitumor and Immunomodulatory Effects of Polysaccharides from Broken-Spore of Ganoderma lucidum. Front Pharmacol. 2012;3:135.
13. Chang YH, Yang JS, Yang JL, et al. Gandoderma lucidum extract promotes immune responses in normal BALB/c mice In vivo. In Vivo. 2009 Sep-Oct;23(5):755-9.
14. Chen WY, Yang WB, Wong CH, et al. Effect of Reishi polysaccharides on human stem/progenitor cells. Bioorg Med Chem. 2010 Dec 15;18(24):8583-91.
15. Ji Z, Tang Q, Zhang J, et al. Immunomodulation of bone marrow macrophages by GLIS, a proteoglycan fraction from Lingzhi or Reishi medicinal mushroom Ganoderma lucidium (W.Curt.:Fr.) P. Karst. Int J Med Mushrooms. 2011;13(5):441-8.
16. Ruan W, Wei Y, Popovich DG. Distinct Responses of Cytotoxic Ganoderma lucidum Triterpenoids in Human Carcinoma Cells. Phytother Res. 2015 Nov;29(11):1744-52.
17. Pan K, Jiang Q, Liu G, et al. Optimization extraction of Ganoderma lucidum polysaccharides and its immunity and antioxidant activities. Int J Biol Macromol. 2013 Apr;55:301-6.
18. Choi S, Nguyen VT, Tae N, et al. Anti-inflammatory and heme oxygenase-1 inducing activities of lanostane triterpenes isolated from mushroom Ganoderma lucidum in RAW264.7 cells. Toxicol Appl Pharmacol. 2014 Nov 1;280(3):434-42.
19. Chijioke O, Landtwing V, Munz C. NK Cell Influence on the Outcome of Primary Epstein-Barr Virus Infection. Front Immunol. 2016;7:323.
20. Novakova L, Lehuen A, Novak J. Low numbers and altered phenotype of invariant natural killer T cells in recurrent varicella zoster virus infection. Cell Immunol. 2011;269(2):78-81.
21. Orange JS. Natural killer cell deficiency. J Allergy Clin Immunol. 2013 Sep;132(3):515-25.
22. Vivier E, Tomasello E, Baratin M, et al. Functions of natural killer cells. Nat Immunol. 2008 May;9(5):503-10.
23. Jost S, Altfeld M. Control of human viral infections by natural killer cells. Annu Rev Immunol. 2013;31:163-94.
24. Vidal SM, Khakoo SI, Biron CA. Natural killer cell responses during viral infections: flexibility and conditioning of innate immunity by experience. Curr Opin Virol. 2011 Dec;1(6):497-512.
25. Xu M, Muto T, Yabe T, et al. The relationship between the frequency of the common cold and the activities of natural killer cells. Environ Health Prev Med. 2000 Jan;4(4):212-6.
26. Hazeldine J, Lord JM. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013 Sep;12(4):1069-78.
27. Ongradi J, Kovesdi V. Factors that may impact on immunosenescence: an appraisal. Immun Ageing. 2010 Jun 14;7:7.
28. Fuentes E, Fuentes M, Alarcon M, et al. Immune System Dysfunction in the Elderly. An Acad Bras Cienc.2017 Jan-Mar;89(1):285-99.
29. Eo SK, Kim YS, Lee CK, et al. Possible mode of antiviral activity of acidic protein bound polysaccharide isolated from Ganoderma lucidum on herpes simplex viruses. J Ethnopharmacol. 2000 Oct;72(3):475-81.
30. Avtonomova AV, Krasnopolskaya LM. Antiviral properties of basidiomycetes metabolites. Antibiot Khimioter. 2014;59(7-8):41-8.
31. Akihisa T, Nakamura Y, Tagata M, et al. Anti-inflammatory and anti-tumor-promoting effects of triterpene acids and sterols from the fungus Ganoderma lucidum. Chem Biodivers. 2007 Feb;4(2):224-31.
32. Iwatsuki K, Akihisa T, Tokuda H, et al. Lucidenic acids P and Q, methyl lucidenate P, and other triterpenoids from the fungus Ganoderma lucidum and their inhibitory effects on Epstein-Barr virus activation. J Nat Prod. 2003 Dec;66(12):1582-5.
33. Li Y, Yang Y, Fang L, et al. Anti-hepatitis activities in the broth of Ganoderma lucidum supplemented with a Chinese herbal medicine. Am J Chin Med. 2006;34(2):341-9.
34. Li YQ, Wang SF. Anti-hepatitis B activities of ganoderic acid from Ganoderma lucidum. Biotechnol Lett. 2006 Jun;28(11):837-41.
35. Lu YZ, Wu XX, Chen S, et al. Effectiveness of Ganoderma lucidum preparation in treating simian acquired immune deficiency syndrome. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2011 Jun;33(3):318-24.
36. Akbar R, Yam WK. Interaction of ganoderic acid on HIV related target: molecular docking studies. Bioinformation. 2011;7(8):413-7.
37. Wu Z, Zhang Y, Tan N, et al. ReishiMax extends the lifespan of mice: A preliminary report. The FASEB Journal. 2011 April 1, 2011;25(1 Supplement):601.2.
38. Zhang K, Ma X, He W, et al. Extracts of Cistanche deserticola Can Antagonize Immunosenescence and Extend Life Span in Senescence-Accelerated Mouse Prone 8 (SAM-P8) Mice. Evid Based Complement Alternat Med. 2014;2014:601383.
39. Zhang YH, Wang LC, Tu PF, et al. Macrophage activation by low molecular weight saccharides from Cistanche deserticola. Zhongguo Zhong Yao Za Zhi.2017 Nov;42(21):4207-10.
40. Zhang A, Yang X, Li Q, et al. Immunostimulatory activity of water-extractable polysaccharides from Cistanche deserticola as a plant adjuvant in vitro and in vivo. PLoS One. 2018;13(1):e0191356.
41. Yonei Y, Kitano T, Ogura M, et al. Effects of Health Food Containing Cistanche Deserticola Extract on QOL and Safety in Elderly: An Open Pilot Study of 12-week Oral Treatment. Anti-Aging Medicine. 2011;8(2):7-14.
42. Lee LK, Foo KY. Recent advances on the beneficial use and health implications of Pu-Erh tea. Food Research International. 2013 10//;53(2):619-28.
43. Zhang L, Shao WF, Yuan LF, et al. Decreasing pro-inflammatory cytokine and reversing the immunosenescence with extracts of Pu-erh tea in senescence accelerated mouse (SAM). Food Chem. 2012 Dec 15;135(4):2222-8.
44. Chu SL, Fu H, Yang JX, et al. A randomized double-blind placebo-controlled study of Pu'er tea extract on the regulation of metabolic syndrome. Chin J Integr Med. 2011 Jul;17(7):492-8.
45. Ugarte-Gil MF, Sanchez-Zuniga C, Gamboa-Cardenas RV, et al. Circulating naive and memory CD4+ T cells and metabolic syndrome in patients with systemic lupus erythematosus: data from a primarily Mestizo population. Rheumatology (Oxford). 2015 Jul;54(7):1302-7.
46. Solana R, Tarazona R, Aiello AE, et al. CMV and Immunosenescence: from basics to clinics. Immun Ageing. 2012 Oct 31;9(1):23.
47. Pawelec G, McElhaney JE, Aiello AE, et al. The impact of CMV infection on survival in older humans. Curr Opin Immunol. 2012 Aug;24(4):507-11.
48. Wang GC, Kao WH, Murakami P, et al. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol. 2010 May 15;171(10):1144-52.