Life Extension Magazine®
It is rare for young people to develop cancer, life-threatening infections,1,2 or chronic inflammation.3-5 Why? Their immune systems are operating at peak capacity, turning “on” and “off” at precise times to eradicate pathogens, while not causing the chronic inflammation that can lead to cardiovascular disease and diabetes.6,7
As we age, this picture of health changes rapidly. By then, we have depleted our valuable treasure chest of defensive immunity cells and the balance shifts to a less vigorous immune system.
Serious infections, cancers, and inflammatory diseases are among the leading causes of premature death in older adults.1,8,9 These disorders all arise from a common cause: the aging of the immune system, or immune senescence.10
Immune senescence is now recognized as a major public health threat to aging populations.11-14
Doctors today respond to immune senescence by treating each disease or condition separately.15-17 This approach fails to correct a major underlying mechanism behind both disease and aging and leaves us waiting for the next health problem to manifest.
After researching the causes of immune senescence, scientists have identified two botanicals that can provide powerful, complementary restorative properties that strengthen the two main branches of the immune system through unique mechanisms.
Cistanche primarily targets the adaptive immune system,18 the specialized branch of the system that allows for a stronger immune response tailored to specific pathogens while providing longer-lasting protection.
And the medicinal mushroom Ganoderma lucidum, or Reishi, has potent strengthening effects mainly on the innate immune system,19 the first-line component of the immune system that attacks foreign pathogens, including bacterial organisms, cells infected with viruses, and those transformed into malignant cells.20
Aging individuals need robust function of both adaptive and innate immunity to remain protected against infections, cancers, and inflammatory diseases.21-25 Together, these bioactive agents, cistanche and Reishi, work in a complementary fashion to rejuvenate both major arms of the aging immune system.
Understanding Your Immune System
Let’s take a quick tour of your immune system so that you understand how to best restore it to optimal functioning.
There are two main components of immune function that are intimately interconnected and work together to deliver round-the-clock surveillance and defense against body invasion.
Immune senescence involves the gradual loss of function of both of these components called the (1) innate and the (2) adaptive branches.26,27 Normally, both branches of the immune system work closely together, with the innate immune system taking the initial lead in defending the body against infection.28
1) Innate immunity is the first line of defense to neutralize a foreign threat in the form of a bacterium, a virally infected cell, or a cell that has undergone malignant transformation early in the development of a cancer.29,30
While the innate immune system is launching its first attacks, the adaptive immune system starts to ramp up its targeted defenses that include “smart” weapons like antibodies against specific organisms and the group of immune system cells known as T-cells.31,32
2) Adaptive immunity, with its heavy reliance on T-cells, begins to fade surprisingly early in life. The primary source of T-cells, the thymus gland in the chest, begins to shrink by young adulthood, making new, naïve T-cells increasingly rare.11,33-35
Boost The Immune System To Increase Life Span
- Immune senescence, or aging of the immune system, is a key underlying cause of symptoms of aging, such as influenza, pneumonia, and a host of viral, bacterial, and fungal diseases.
- Reduced function of your immune system also predisposes you to cancer and autoimmune disorders, both of which require functioning immunity to keep at bay.
- Taken together, the results of immune senescence contribute to exaggerated rates of early death.
- You can fight the impact of immune senescence in your own body by addressing the two major divisions of the immune system.
- Extracts of Reishi primarily restore vigor and normal function to the innate branch of the immune system, the inborn system responsible for the immediate, nonspecific responses to threats that allow your body to fend off previously unseen organisms and abnormal cells.
- Extracts of the herb Cistanche primarily boost the highly modulated adaptive branch of the immune system responsible for longer-term, more specific responses to threats and provide swift responses when you are re-exposed to a threat your body has “seen” previously.
- Both of these natural supplements have been shown to prolong life in animal studies, and both produce immune-boosting functions in human trials.
- Both innate and adaptive immunity can be strengthened with this combination of healing herbs, now shown to have effects demonstrable by modern immunological assays.
The Importance Of T-Cells
T-cells can be considered the “brains” of the immune system.32 The immune system includes two types of T-cells: naïve T-cells and memory T-cells.36 These two types of T-cells allow the body to produce specific responses to new and repeating threats. Without T-cells, any minor infection such as a cold or a minor cut could ultimately result in death.
Naïve T-cells, which are abundant in our young life, respond to new threats that occur to the body. However, once they have responded to a specific virus or bacteria, they “learn” the molecular pattern of this threat and convert to memory T-cells. These memory T-cells are like a stored number on your cell phone; they are programmed to respond to a specific threat that has previously invaded the body.11 These memory T-cells are now programmed to respond to known threats, but will not rally to head off a new, unknown threat.
So, for example, if you catch the flu as a child, your body will send out a fleet of naïve T-cells to attack and mop up the infection. As an adult, if you are exposed to a similar flu virus again, your body will send out a fleet of memory T-cells to prevent the infection.
As we age, we build up an increasing inventory of memory T-cells that have “memories” of previous infections, which allows them to respond quickly to a similar invasion.
Unfortunately, as we build up this inventory of memory T-cells, we also deplete our inventory of naïve T-cells.37 This depletion can have tragic results as we age. With fewer naïve T-cells to respond to new attackers, the body can become vulnerable and quickly devastated. The body will increasingly respond only to “known and repeated” threats and overlook “new” threats.11 It seems with each passing day there are new threats emerging, such as new strains of flu or nascent cancer cells for which we must be prepared. 31,38,39
Fortunately, two botanicals, Cistanche and Reishi can provide a powerful, natural means of boosting both adaptive and innate immunity. Each of these bioactives works in a unique and complementary fashion to stimulate the two key factors in a waning immune system.
Chronic Viral Infection Worsens Immune Senescence
An important but little-regarded viral infection has now been found to contribute to accelerated immune senescence in a large number of aging adults. Cytomegalovirus, or CMV, is a member of the herpes virus family that embeds itself in T-cells, where like a computer virus, it “runs in the background,” using up cellular resources while weakening the effectiveness of the immune system as a whole.35
Older adults who test positive for CMV in their blood have a significantly higher immune risk profile than do uninfected people, which puts them at increased risk of early death related to immune senescence.72 Studies reveal that chronic CMV infection, which typically produces no detectable symptoms, is strongly associated with an accumulation of weakened memory T-cells, and a concomitant reduction in the naïve T-cells necessary to cope with new infectious or malignant threats.72
And CMV-infected people die earlier: One study found a 42% increase in the annual death rate among older adults with CMV compared to those without, corresponding to a 3.7-year reduction in life expectancy after age 65.73 Conversely, members of very long-lived families appear to have better control of the virus and these people, even when CMV infected, have fewer of the T-cell abnormalities associated with immune senescence, and thereby live longer.72
While there is little you can do to prevent or directly treat CMV infection, you can fight its deleterious effects on your longevity by doing all you can to boost your adaptive and innate immune systems using natural supplements such as Reishi and Cistanche extracts (and if need be customized prescription drug regimens).
Cistanche: Support For Adaptive Immunity
Extracts of the Cistanche plant species have been used for thousands of years as a tonic for a variety of age-related disorders.40,41 In Traditional Chinese Medicine, Cistanche is used for its perceived ability to promote immune function in older people, which is now being proven by today’s scientific understanding of immune senescence.18
Cistanche extracts have broad-spectrum benefits for the immune system, with the bulk of their effects producing favorable changes in age-related adaptive immunity.
One of the major components found in Cistanche species is echinacoside, which stimulates the creation of T-cells 42 and enhances cell survival by reducing apoptosis.43
Echinacoside increases the expression of a vital growth factor that benefits immune function by potentially suppressing the premature conversion of naïve T-cells into activated memory T-cells.43-48 This is important because as we age, our naïve T-cells dwindle in numbers, which reduces our protective immune function.
But now there is a way to help increase the dwindling pool of naïve T-cells needed for later responses to new threats. 18,45,46 Cistanche raises levels of a growth factor that not only promotes increases in naïve T-cells, but has also been studied as a novel approach to minimizing the autoimmune response so common in immune senescence.45,49
As we age, our immune systems are less able to properly control inflammatory responses.50 Normally, our regulatory immune cells shut down inflammation at an appropriate time. With the onset of immune senescence, these regulatory cells lose their potency and tissues normally protected against inflammation become vulnerable to an ongoing attack by inflammatory cells. This component of immune senescence is responsible for persistent inflammation in autoimmune diseases such as lupus (where connective tissue is attacked), rheumatoid arthritis (where joint lining tissue is attacked), and inflammatory bowel diseases (where intestinal lining tissue is attacked).51,52
Increased Life Span With Cistanche
One of the most comprehensive and exciting outcomes of recent Cistanche research has been in the promotion of longevity. These studies indicate that enhancing immune function in older organisms prolongs life span.
A recent study looked at the use of Cistanche extracts as a way to delay aging. In the study, mice were given four weeks of supplementation with Cistanche extracts containing 8.25% by weight echinacoside. The scientists found that Cistanche extracts extended life span.18 The subjects of this study were a special strain of “senescence-accelerated mice,” which age at a much faster rate than do normal mice, making them ideal for aging studies.
The control mice that were not treated with Cistanche extracts survived up to 385 days. In the treated group, 40% of the Cistanche-supplemented animals remained alive!18 The untreated control mice had an average life span of 325 days, which is significantly shorter than the Cistanche group (375 days).
The reasons for this longevity factor became apparent as researchers examined the immune cells. The control mice who did not take Cistanche extracts had an abundance of poorly functioning memory T-cells, like most aging humans. The mice also had low numbers of naïve T-cells.
The Cistanche-supplemented animals that were on a low-dose human equivalent to 210 mg/day had increases in naïve T-cells and had lower populations of memory T-cells, which is similar to a youthful immune system that is highly functional. What the study tells us is that the mice given Cistanche extracts had more immunological reserve and potentially were better “primed” for dealing with new threats to their longevity.
This study also provided evidence that Cistanche extracts have beneficial effects on innate immunity as well, by boosting levels of natural killer (NK) cells and reducing levels of the pro-inflammatory cytokine interleukin-6 (IL-6).18
We can now connect the dots between animal and human studies with Cistanche.
Protecting Human Immunity
In a study from Japan, healthy older men and women (aged 65 to 80 years) were supplemented for 12 weeks with Cistanche extracts (containing 8.5% by weight echinacoside) in a nutritional formulation.53 Scientists found impressive gains in immune factors after supplementation. Subjects in this study had significant increases of 11.7% in natural killer (NK) cell activity (components of innate immunity), which offer protection against new invaders. The researchers also showed a 20.2% increase in the ratio of beneficial CD4 T-cells to CD8 T-cells. An increased CD4/CD8 ratio is indicative of healthy, youthful immune function.
This human study, taken together with the previous animal studies, provides a link between enhanced immunity and longevity. It can be assumed that boosting adaptive immunity with Cistanche extracts may assist in prolonging human life span.
Using Immune-Boosting Supplements
Boosting your immune function by enhancing both innate and adaptive immunity is clearly beneficial.
Comprehensive support for both adaptive and innate immunity may be achieved with the use of standardized Cistanche and Reishi extracts all year-round.
Reishi Extract: Enhancing Innate Immunity
Boosting adaptive immunity is only half of the story in managing immune senescence. To have a successful immune system, you also need an active innate immune response in order to fully identify and destroy threats from infections, malignancies, and out-of-control inflammation. Remember, without a strong, nonspecific innate immune response, your body won’t have time to develop the adaptive immunity you need to survive new threats.
Reishi mushrooms (Ganoderma lucidum) are well known in Asian traditional medicine, with multiple uses for promotion of health and longevity.54,55 Working in a way that is complementary to Cistanche, Reishi extracts enhance the innate immune system, boosting the function of its components to prevent premature aging and death.
This was shown dramatically in a study of healthy adult mice.56 At the age of one year (which is middle age for a mouse), the animals were fed either control chow without supplementation, or chow enriched with Reishi extracts. By 88 weeks of life (old age), the average age of survivors (when half the animals in each group had died) was up to 66 days longer in Reishi-supplemented mice than in control animals. At the point when only 20% of mice survived, the Reishi-supplemented mice were up to 110 days older on average than were control mice, while by the time only 10% survived, the remaining Reishi-supplemented animals were up to 148 days older or more than controls.
In other words, it took significantly longer for the Reishi-supplemented mice to be negatively impacted by the effects of aging. The bottom line is that the surviving mice who took Reishi were older than their unsupplemented peers.
Reishi’s life-extending effects on boosting immunity include enhancements to:57-59
- Cytotoxic T-cells that attack and kill aberrant cells that can’t provide proper identification as part of one’s “self”, such as virus-infected cells or cells that may be turning malignant.
- Neutrophils, which blast invaders with destructive chemical bursts,
- Cytokines, signaling molecules that draw in attack cells,
- Toll-like receptors, which are molecular pattern-detection receptors on immune cells that identify dangerous molecular patterns carried by pathogens,
- Major histocompatibility (MHC) interactions that distinguish between human tissue types and foreign materials; their enhancement reduces malignant cells’ ability to hide from the immune system.60
Reishi extracts also reduce secretion of the pro-inflammatory cytokine IL-6; high levels of IL-6 in human populations is closely associated with shorter life spans.55,61,62
On the other hand, Reishi enhances production of interleukin-10 (IL-10), the cytokine associated with greater longevity in human studies.51,61,63 Additionally, Reishi regulates the innate immune response by suppressing TNF-alpha, which is a major pro-inflammatory signaling molecule.55,61
Reishi extracts have been shown to stimulate cell-killing activity by modulating dendritic cells, which is important since these cells help eradicate both virus infected and malignant cells.59 And polysaccharides from Reishi enhances two major features of innate immune system cells: phagocytosis (engulfing and destroying microorganisms) and chemotaxis (movement of attack cells towards a threatening invader).64
All of these innate immunity-boosting properties come to fruition in studies of Reishi as an antiviral agent. Polysaccharides from Reishi are especially effective against viruses in the herpesvirus family, which includes herpes simplex viruses responsible for oral/genital herpes and shingles, respectively.65,66 Another herpesvirus, cytomegalovirus, is responsible for many of the features of immune senescence that accelerate aging and reduce longevity.
Human studies are beginning to show potent antiherpesvirus effects from Reishi. People infected with herpes zoster viruses may suffer from post-herpetic neuralgia, a severely painful nerve disorder that can linger for years as a result of the virus taking refuge in nerve cells. In an early proof-of-concept study, patients who did not respond to standard treatment, as well as those with painful shingles outbreaks, experienced dramatic reduction in pain using Reishi.67
In fact, Reishi extracts reduce viral, bacterial, and parasitic organisms sufficiently well and have been used as natural additives to the feed of a variety of animals and birds.68-71 In one study, extracts from the mushroom stimulated innate immunity by activating bacteria-engulfing cells called macrophages to devour the human pathogen Listeria monocytogenes.69
Summary
Aging of the immune system, or immune senescence, is a major component of systemic aging and a leading cause of life-shortening diseases of aging such as infectious diseases, malignancies, and chronic inflammatory disorders.
Immune senescence encompasses cumulative deficits in the innate, or first-line, branch of the immune system, accounting for difficulties older adults have in fending off new, previously unseen threats like emerging viruses or developing cancer cells.
But immune senescence also involves deficits in the adaptive, or “teachable” branch of the immune system, which is why older adults respond poorly to vaccines and may experience recurrence of diseases that their bodies had previously encountered.
Two immune-boosting botanical extracts—from Cistanche herbs and from Reishi mushrooms—have now been shown to exert powerful and complementary effects on the innate and the adaptive immune systems. Both supplements increase longevity in animal studies, presumably related to the impact of Cistanche mainly on adaptive immunity and to Reishi’s impact mainly on innate immunity.
We can’t ignore the lethal impact that immune senescence inflicts on our aging bodies. Increased susceptibility to bacterial, viral, and fungal infections, to cancer development, and to autoimmune/inflammatory diseases are all manifestations of immune senescence. All can shorten our life spans.
Exciting studies of Cistanche and Reishi extracts show how they can help restore youthful immune function.
If you have any questions on the scientific content of this article, please call a Life Extension® wellness specialist at 1-866-864-3027.
Editor's Note
Science continues to evolve, and new research is published daily. As such, we have a more recent article on this topic: Combat Immune Senescence
References
- Werner H, Kuntsche J. Infection in the elderly—what is different? Z Gerontol Geriatr. 2000 Oct;33(5):350-6.
- Holloway WJ. Management of sepsis in the elderly. Am J Med. 1986 Jun 30;80(6B):143-8.
- Candore G, Caruso C, Jirillo E, Magrone T, Vasto S. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Curr Pharm Des. 2010;16(6):584-96.
- Bartlett DB, Firth CM, Phillips AC, et al. The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection. Aging Cell. 2012 Oct;11(5):912-5.
- Baylis D, Bartlett DB, Patel HP, Roberts HC. Understanding how we age: insights into inflammaging. Longev Healthspan. 2013 May 2;2(1):8.
- Available at: http://my.americanheart.org/professional/sciencenews/a-lifelong-perspective-on-the-cardiovascular-toxicity-of-cancer-therapy-in-ch_ucm_454391_article.jsp. Accessed September 29, 2014.
- Laitinen OH, Honkanen H, Pakkanen O, et al. Coxsackievirus B1 is associated with induction of β-cell autoimmunity that portends type 1 diabetes. Diabetes. 2014 Feb;63(2):446-55.
- Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90.
- Hansen J. Common cancers in the elderly. Drugs Aging. 1998 Dec;13(6):467-78.
- Ongrádi J, Kövesdi V. Factors that may impact on immunosenescence: an appraisal. Immun Ageing. 2010 Jun 14;7:7.
- Pawelec G. Hallmarks of human “immunosenescence”: adaptation or dysregulation? Immun Ageing. 2012;9(1):15.
- 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.
- Hakim FT, Gress RE. Immunosenescence: deficits in adaptive immunity in the elderly. Tissue Antigens. 2007 Sep;70(3):179-89.
- Larbi A, Fülöp T, Pawelec G. Immune receptor signaling, aging and autoimmunity. Adv Exp Med Biol. 2008;640:312-24.
- Aliberti S, Kaye KS. The changing microbiologic epidemiology of community-acquired pneumonia. Postgrad Med. 2013 Nov;125(6):31-42.
- Nazarko L. Recurrent urinary tract infection in older women: an evidence-based approach. Br J Community Nurs. 2013 Aug;18(8):407-8,102.
- Olaya-Abril A, Prados-Rosales R, McConnell MJ, et al. Characterization of protective extracellular membrane-derived vesicles produced by Streptococcus pneumoniae. J Proteomics. 2014 Jun 25;106:46-60.
- 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. J Evid Based Complementary Altern Med. 2014;2014:601383.
- Xu Z, Chen X, Zhong Z, Chen L, Wang Y. Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities. Am J Chin Med. 2011;39(1):15-27.
- Rabb H. The T cell as a bridge between innate and adaptive immune systems: implications for the kidney. Kidney Int. 2002 Jun;61(6):1935-46.
- O’Sullivan T, Saddawi-Konefka R, Vermi W, et al. Cancer immunoediting by the innate immune system in the absence of adaptive immunity. J Exp Med. 2012 Sep 24;209(10):1869-82.
- Acres B, Gantzer M, Remy C, et al. Fusokine interleukin-2/interleukin-18, a novel potent innate and adaptive immune stimulator with decreased toxicity. Cancer Res. 2005 Oct 15;65(20):9536-46.
- Pawelek KA, Huynh GT, Quinlivan M, Cullinane A, Rong L, Perelson AS. Modeling within-host dynamics of influenza virus infection including immune responses. PLoS Comput Biol. 2012;8(6):e1002588.
- Lessard CJ, Li H, Adrianto I, et al. Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome. Nat Genet. 2013 Nov;45(11):1284-92.
- Chew T, Taylor KE, Mossman KL. Innate and adaptive immune responses to herpes simplex virus. Viruses. 2009 Dec;1(3):979-1002.
- Busse PJ, Mathur SK. Age-related changes in immune function: effect on airway inflammation. J Allergy Clin Immunol. 2010 Oct;126(4):690-9; quiz 700-1.
- Agarwal S, Busse PJ. Innate and adaptive immunosenescence. Ann Allergy Asthma Immunol. 2010 Mar;104(3):183-90; quiz 190-2, 210.
- Rasmussen SB, Reinert LS, Paludan SR. Innate recognition of intracellular pathogens: detection and activation of the first line of defense. APMIS. 2009 May;117(5-6):323-37.
- Si-Tahar M, Touqui L, Chignard M. Innate immunity and inflammation--two facets of the same anti-infectious reaction. Clin Exp Immunol. 2009 May;156(2):194-8.
- Woods JA, Davis JM, Smith JA, Nieman DC. Exercise and cellular innate immune function. Med Sci Sports Exerc. 1999 Jan;31(1):57-66.
- Priest SO, Baumgarth N. The role of innate signals in B cell immunity to influenza virus. Front Biosci (Schol Ed). 2013;5:105-17.
- Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Chapter 24, The Adaptive Immune System.
- Moro-Garcia MA, Alonso-Arias R, Lopez-Larrea C. When aging reaches CD4+ T-Cells:phenotypic and functional changes. Front Immunol. 2013;4:107.
- Palmer DB. The effect of age on thymic function. Front Immunol. 2013;4:316.
- Brunner S, Herndler-Brandstetter D, Weinberger B, Grubeck-Loebenstein B. Persistent viral infections and immune aging. Ageing Res Rev. 2011 Jul;10(3):362-9.
- Tough DF, Sprent J. Life span of naive and memory T cells. Stem Cells. 1995 May;13(3):242-9.
- Pfister G, Weiskopf D, Lazuardi L, et al. Naive T cells in the elderly: are they still there? Ann N Y Acad Sci. 2006 May;1067:152-7.
- Basha S, Hazenfeld S, Brady RC, Subbramanian RA. Comparison of antibody and T-cell responses elicited by licensed inactivated- and live-attenuated influenza vaccines against H3N2 hemagglutinin. Hum Immunol. 2011 Jun;72(6):463-9.
- Gasparini R, Amicizia D, Lai PL, Panatto D. Aflunov((R)): a prepandemic influenza vaccine. Expert Rev Vaccines. 2012 Feb;11(2):145-57.
- Shi HM, Wang J, Wang MY, Tu PF, Li XB. Identification of Cistanche species by chemical and inter-simple sequence repeat fingerprinting. Biol Pharm Bull. 2009 Jan;32(1):142-6.
- Gu L, Xiong WT, Wang C, Sun HX, Li GF, Liu X. Cistanche deserticola decoction alleviates the testicular toxicity induced by hydroxyurea in male mice. Asian J Androl. 2013 Nov;15(6):838-40.
- Zhai Z, Liu Y, Wu L, et al. Enhancement of innate and adaptive immune functions by multiple Echinacea species. J Med Food. 2007 Sep;10(3):423-34.
- Jia Y, Guan Q, Guo Y, Du C. Echinacoside stimulates cell proliferation and prevents cell apoptosis in intestinal epithelial MODE-K cells by up-regulation of transforming growth factor-beta1 expression. J Pharmacol Sci. 2012;118(1):99-108.
- Kim MT , Harty JT. Impact of Inflammatory cytokines on effector and memory CD8+ T cells. Front Immunol. 2014 Jun 19;5:295.
- Kapitein B, Tiemessen MM, Liu WM, et al. The interleukin-10 inducing effect of transforming growth factor-beta on human naive CD4+ T cells from cord blood is restricted to the TH1 subset. Clin Exp Immunol. 2007 Feb;147(2):352-8.
- Filippi CM, Juedes AE, Oldham JE, et al. Transforming growth factor-beta suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity. Diabetes. 2008 Oct;57(10):2684-92.
- Takai S, Tokuda H, Matsushima-Nishiwaki R, Saio M, Takami T, Kozawa O. TGF-beta superfamily enhances the antigen-induced IFN-gamma production by effector/memory CD8+ T cells. Int J Mol Med. 2010 Jan;25(1):105-11.
- Takai S, Schlom J, Tucker J, Tsang KY, Greiner JW. Inhibition of TGF-β1 signaling promotes central memory T cell differentiation. J Immunol. 2013 Sep 1;191(5):2299-307.
- Gorelik L, Flavell RA. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity. 2000 Feb;12(2):171-81.
- Wong CP, Magnusson KR, Ho E. Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation. J Nutr Biochem. 2013 Jan;24(1):353-9.
- Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol. 2013 May;14(5):428-36.
- Salvioli S, Monti D, Lanzarini C, et al. Immune system, cell senescence, aging and longevity--inflamm-aging reappraised. Curr Pharm Des. 2013;19(9):1675-9.
- Yonei Y, Kitano T, Ogura M, et al. Effects of health food containing Cistanche deserticola extract on QOL and safety in ederly: an open pilot study of 12-week oral treatment. J Anti-Aging Med. 2011;8(2):7-14.
- Lin YL, Liang YC, Tseng YS, et al. An immunomodulatory protein, Ling Zhi-8, induced activation and maturation of human monocyte-derived dendritic cells by the NF-kappaB and MAPK pathways. J Leukoc Biol. 2009 Oct;86(4):877-89.
- Dudhgaonkar S, Thyagarajan A, Sliva D. Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol. 2009 Oct;9(11):1272-80.
- Wu Z, Zhang Y, Tan N, Zhao C, Yang J, Zhu J-S. ReishiMax extends the lifespan of mice: A preliminary report. The FASEB Journal. 2011;25(601.2).
- Batbayar S, Kim MJ, Kim HW. Medicinal mushroom Lingzhi or Reishi, Ganoderma lucidum (W.Curt.:Fr.) P. Karst., beta-glucan induces Toll-like receptors and fails to induce inflammatory cytokines in NF-kappaB inhibitor-treated macrophages. Int J Med Mushrooms. 2011;13(3):213-25.
- Kuan YC, Sheu F, Lee GC, Tsai MW, Hung CL, Nan FH. Administration of recombinant Reishi immunomodulatory protein (rLZ-8) diet enhances innate immune responses and elicits protection against nervous necrosis virus in grouper Epinephelus coioides. Fish Shellfish Immunol. 2012 Jun;32(6):986-93.
- Cao LZ, Lin ZB. Regulatory effect of Ganoderma lucidum polysaccharides on cytotoxic T-lymphocytes induced by dendritic cells in vitro. Acta Pharmacol Sin. 2003 Apr;24(4):321-6.
- Sun LX, Lin ZB, Duan XS, et al. Enhanced MHC class I and costimulatory molecules on B16F10 cells by Ganoderma lucidum polysaccharides. J Drug Target. 2012 Aug;20(7):582-92.
- Pan K, Jiang Q, Liu G, Miao X, Zhong D. Optimization extraction of Ganoderma lucidum polysaccharides and its immunity and antioxidant activities. Int J Biol Macromol. 2013 Apr;55:301-6.
- Wassel CL , Barrett-Connor E, Laughlin GA. Association of circulating C-reactive protein and interleukin-6 with longevity into the 80s and 90s: The Rancho Bernardo Study. J Clin Endocrinol Metab. 2010 Oct;95(10):4748-55.
- Lio D, Scola L, Crivello A, et al. Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun. 2002 Feb;3(1):30-3.
- Hsu MJ, Lee SS, Lee ST, Lin WW. Signaling mechanisms of enhanced neutrophil phagocytosis and chemotaxis by the polysaccharide purified from Ganoderma lucidum. Br J Pharmacol. 2003 May;139(2):289-98.
- Liu J, Yang F, Ye LB, et al. Possible mode of action of antiherpetic activities of a proteoglycan isolated from the mycelia of Ganoderma lucidum in vitro. J Ethnopharmacol. 2004 Dec;95(2-3):265-72.
- Li Z, Liu J, Zhao Y. Possible mechanism underlying the antiherpetic activity of a proteoglycan isolated from the mycelia of Ganoderma lucidum in vitro. J Biochem Mol Biol. 2005 Jan 31;38(1):34-40.
- Hijikata Y, Yamada S. Effect of Ganoderma lucidum on postherpetic neuralgia. Am J Chin Med. 1998;26(3-4):375-81.
- Ogbe AO, Atawodi SE, Abdu PA, Sannusi A, Itodo AE. Changes in weight gain, faecal oocyst count and packed cell volume of Eimeria tenella-infected broilers treated with a wild mushroom (Ganoderma lucidum) aqueous extract. J S Afr Vet Assoc. 2009 Jun;80(2):97-102.
- Wang CL, Pi CC, Kuo CW, et al. Polysaccharides purified from the submerged culture of Ganoderma formosanum stimulate macrophage activation and protect mice against Listeria monocytogenes infection. Biotechnol Lett. 2011 Nov;33(11):2271-8.
- Oluba OM, Olusola AO, Fagbohunka BS, Onyeneke E. Antimalarial and hepatoprotective effects of crude ethanolic extract of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.)P.Karst. (higher Basidiomycetes), in Plasmodium berghei-infected mice. Int J Med Mushrooms. 2012;14(5):459-66.
- Zhang W, Tao J, Yang X, et al. Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection. Biochem Biophys Res Commun. 2014 Jul 4;449(3):307-12.
- Derhovanessian E, Maier AB, Beck R, et al. Hallmark features of immunosenescence are absent in familial longevity. J Immunol. 2010 Oct 15;185(8):4618-24.
- Savva GM, Pachnio A, Kaul B, et al. Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell. 2013 Jun;12(3):381-7.