How immune decline hastens aging.
A concern expressed by our older members is whether they can remain alive long enough to benefit from the upcoming biomedical revolution. These health activists want to determine their areas of vulnerability to ensure they're not overlooking a validated way to stave off disease, aging, and death.
Our work involving longevity research dates back to the 1960s. This has enabled us to gain exclusive insights into what causes people to die-people who otherwise take exceptionally good care of themselves.
A sad example of mortality vulnerability occurred in January 2014. That's when one of our pioneer members died at the young age of 92. His intellectual contributions, spanning many decades, helped us survive withering governmental assaults aimed at censoring our ability to disseminate lifesaving information.
I can't stop thinking that we were only weeks away from potentially saving him. I don't want this same fate to befall other Life Extension[R] members.
We've talked before about the lethal impact of immune senescence. It occurs when our aging immune system fails to protect against cancers/infections, and instead generates excess inflammatory reactions that attack every cell in our body.
What virtually no one understands is how aging accelerates immune decline and what must be done to reverse this lethal trend.
The most common afflictions associated with normal aging are atherosclerosis, cancer, and Alzheimer's disease. (1) What few doctors know is that all these illnesses are related to immune senescence. (2,3)
In people over age 65, the top 10 causes of death include pneumonia, influenza, and sepsis (systemic inflammation caused by severe infection). (1) Immune senescence is a major cause of all these maladies. (4-10)
As winter sets in, the term "immune system" is liberally tossed around as people seek to protect against viral infections. What the public does not yet understand is what causes our immune system to fail as we age. (11)
Why Young Children Catch So Many Colds
Young children get lots of colds. Some suffer as many as eight to ten each year before age 2. (12)
The reason youngsters suffer more colds than older children and adults is because they haven't built up "immunity" to cold viruses. (12) But what does this immunity really mean?
When one is exposed to an infectious agent, the body creates and maintains "memory T-cells" that provide a degree of immunity to the same infection. (13) This works magnificently well in our first four to five decades of life. But then something happens that leads to the downward spiral of immune senescence.
Too Many "Memory T-Cells"
Memory T-cells form when our immune system successfully eradicates an invader. They remain in the body and are ready to instantly respond when that same bacteria, virus, or cancer cell reappears.
One would think it desirable to have lots of memory T-cells. The problem is that memory T-cells only work against prior infections. As we age, we collect excess numbers of memory T-cells and produce fewer critically important naive T-cells. (14)
The term "naive" may not sound like something beneficial as it relates to immune function, but it is. A naive immune cell is one that has not been activated by an antigen (a substance that provokes an adaptive immune response). Since it is "naive" (not yet exposed to an antigen), naive immune cells are primed to effectively respond to new infectious agents and malignancies. (15)
Once exposed, naive immune cells become memory cells or plasma cells specific to the original antigen. As our internal reservoir of naive immune cells is decreased, we have less ability to respond to new infections and malignancies. (16)
To make matters worse, excess numbers of senescent memory cells provoke undesirable inflammatory reactions (17-21) that are thought to underlie most age-related diseases including atherosclerosis, cancer, and dementia. (22-26)
To put this in simplistic terms, if we are to protect against the ravages of immune senescence, we need to increase our numbers of naive cells ("virgin" immune cells), while reducing numbers of surplus senile memory cells.
Importance Of "Functional" Natural Killer Cells
The first line of defense against virus-infected (28-31) and cancer cells is our natural killer cells. (32-45) Young individuals have high levels of functional natural killer (NK) immune cells, but this declines with aging. (46-49)
In elderly subjects, decreased NK cell activity is associated with an increased incidence and severity of viral infections such as shingles, influenza, and cytomegalovirus (CMV). (47,50-53)
Shingles occurs when our immunity to dormant chickenpox viral infection declines. It manifests as an extremely painful skin lesion that can last for months. (54)
Influenza, commonly called the flu, is a virus that inflicts its lethal effects mostly on the elderly, who represent the largest portion of the population that suffers immune dysfunction. (1,7)
Cytomegalovirus (CMV) is a chronic infection that, as you'll discover later in this issue, may contribute significantly to degenerative disease. About 90% of older people showed history of CMV infection on lab testing compared to about 60% of the general population. (55) Increased prevalence of CMV in the elderly is thought to lead to decreased immune surveillance. (56-61)
Natural killer cells originate in the bone marrow (like other immune cells) and go through a maturation process that enables them to participate in early control of microbial infections and cancers. (47,62)
Healthy NK function is critical in eliminating transformed cancer cells. (27,44,63) NK cells are also involved in the elimination of senescent cells (62,64) that otherwise cause chronic inflammation. (27,65-67)
The age-related decrease in functional NK cells is likely to have wider implications for the health of older adults than currently understood by the mainstream. If an aging person is to better manage debilitating and deadly infections and malignancies, maintaining youthful NK function is critical.
"In elderly subjects, decreased NK cell activity has been shown to be associated with an increased incidence and severity of viral infection, highlighting the clinical implications that age-associated changes in NK cell biology have on the health of older adults ... Evidence has emerged that has shown that in addition to eliminating transformed cells, NK cells are involved in many other biological processes such as immune regulation, antimicrobial immune responses, and the recognition and elimination of senescent cells ... Thus, the decrease in NK cell function that accompanies physiological aging is likely to have wider implications for the health of older adults than originally thought." (27)
Reference: Aging Research Reviews-May 6, 2013. "The Impact of Aging on Natural Killer Cell Function and Potential Consequences for Health in Older Adults."
Consequences Of Immune Cell Exhaustion
Over the course of our lifetime, our immune system becomes "exhausted." What this refers to is the excess accumulation of worn-out memory T-cells and reduced production of vital naive T-cells. (68-70)
As people accumulate exhausted T-cells, an adverse consequence is these senile memory cells emit pro-inflammatory cytokines (22,11) that exacerbate chronic inflammatory conditions. (72,73) Individuals with higher levels of exhausted immune cells suffer greater mortality. (74,75)
The deficit of naive immune cells combined with overaccumulation of exhausted memory cells decreases the efficacy (antibody response) of vaccinations. (76-78)
Exhausted memory T-cells are associated with increased inflammation. (79) Inflammation is associated with increased risk of coronary heart disease, impaired vascular function, vascular inflammation, and endothelial dysfunction. (80-83)
An accumulation of exhausted T-cells has been seen in persons suffering from rheumatoid arthritis (84) and ankylosing spondylitis (an inflammatory disease of the spine). (85-87)
Compelling evidence points to the accumulation of senile (exhausted) T-cells as a factor that accelerates a broad array of age-associated diseases. (71)
More T-Helper Cells Needed
T-helper cells identify and tag invaders for elimination by the immune system. (89)
Regulatory T-cells tell the immune system that its job is finished and it's time to stop the attack. (89-91) A normal balance involves having at least one to four T-helper cells for each regulatory T- cell (regulatory T-cells are sometimes called suppressor T-cells). (92)
As humans age, there is an inversion in the T-helper/regulatory T-cell ratio. (93) What this means is that too many regulatory T-cells form while T-helper cell counts drop, resulting in there being more regulatory T-cells than T-helpers. The T-helper/regulatory T-cell ratio can be considered to be a predictor of mortality. (76,77,94) People with low T-helper counts and higher regulatory T-cell counts die sooner.
Cancer patients often present with a low T-helper/regulatory T-cell ratio. (95,96) Some studies show that tumor cells secrete chemicals that turn up regulatory T-cell formation in order to prevent the immune system from attacking cancer cells. (97-99) Cancer chemotherapy dramatically lowers T-helper counts. (100,101)
To combat immune senescence, it is critical to reverse the inversion of the T-helper/regulatory T-cell ratio. This means boosting T-helper counts while lowering regulatory T-cells.
Reversing Immune Senescence
Immune senescence is a prime cause of debility and mortality.
Fortunately, discoveries in recent years have been shown to help reverse the immune dysfunction that plagues virtually all aging humans (and cancer patients).
Here is a summary of the six underlying causes of immune senescence described in this article:
* Decrease in naive immune T-cells needed to fight new invaders. (93)
* Increase in exhausted memory T-cells that create chronic inflammatory reactions. (93)
* Decrease in functional natural killer (NK) cell activity. (93)
* Thymus gland atrophy that reduces T-cell function and numbers.
* Too many regulatory T-cells and a reduction in T-helper cells.
* Excess production of interleukin-6, a cytokine that promotes inflammation. (102)
"We conclude that chronic heart failure patients show a higher degree of immunosenescence than age-matched healthy controls. T-lymphocyte differentiation and interleukin-6 (IL-6) levels are increased in patients with an advanced clinical status and may contribute to disease impairment through a compromised adaptive immune response due to accelerated aging of their immune system." (88)
Reference: International Journal of Cardiology-July 1, 2014. "Immunosenescence and Inflammation Characterize Chronic Heart Failure Patients With More Advanced Disease."
The good news is that there are proven ways to counteract all six factors involved in senile immune dysfunction.
Most Life Extension members already take zinc and DHEA. There is evidence that these supplements can at least partially restore thymic function vital to transforming immune cells produced in bone marrow to mature T-cells. (103-105) DHEA also helps suppress deadly interleukin-6. (106,107)
A breakthrough in combatting immune senescence has been found in a medicinal plant called cistanche that has been used extensively in China to treat the "ailments of aging." (108) Until recently, doctors would not have understood how cistanche reverses some of the underlying causes of immune senescence.
Supplementation with cistanche has been shown to increase naive T-cells and natural killer (NK) cells while decreasing memory T-cells and pro-inflammatory interleukin-6. (109)
One of the characteristics of people who live over 100 years is a low level of interleukin-6.
A prime reason for the severe immune disorders suffered by the elderly is the marked decrease in naive T-cells and functional natural killer cells, with a concomitant increase in memory T-cells. Cistanche reverses these pathological trends that characterize immune senescence.
One way cistanche functions is by restoring the progenitors of peripheral naive T-cells, which explains the increase seen in these vital cells in response to cistanche. (109) Animals supplemented with cistanche have increased life spans, as would be expected by a compound that counteracts immune senescence. (109)
Cistanche is one of the most popular Chinese herbal medicines and is listed in the Chinese herbal pharmacopeias as having "anti-aging" properties.
One reason the Chinese saw such impressive therapeutic results is that cistanche restores one of the most prominent bone marrow biomarkers of immune cell formation called stem cell antigen-1. (109) Senile bone marrow loses its ability to produce fresh naive immune cells, which are launched into the bloodstream to differentiate into mature naive T and natural killer cells. Bone marrow stem cell antigen-1 represents the body's main source of naive T-cells in the blood. (109) Cistanche appears to have a rejuvenating effect on the bone marrow, something that is now only possible using very expensive recombinant drugs. (110-112)
There are other factors that weaken immune function in the elderly that cistanche has been shown to counteract. These will be described in depth in an article appearing in this issue.
Perhaps the most exciting finding was an open-label pilot trial of elderly people that combined a low-dose of cistanche (100 mg) with zinc, vitamin E, vitamin B6, fucoidan, and coenzyme Q10. Not only were markers of immune senescence reversed, but the test subjects reported improvements in quality of life, such as not "feeling tired all the time." This makes sense in light of the multiple adverse effects immune senescence inflicts on the body, which includes increased levels of frailty. (113,114)
How To Take Advantage Of Novel Immune Restorative Technologies
Unlike prescription drugs or even certain dietary supplements, cistanche does not cost a lot. It has been added to the most popular nutrient members now take to bolster immune function (Reishi). Virtually every person over 35 should add this cistanche/Reishi immune protection duo to their daily regimen.
Another supplement to consider for short-term use is enzymatically modified rice bran, which has been demonstrated to have overwhelming benefits in boosting natural killer cell activity. (130,134) The problem we have with this supplement is its high cost. What we are going to suggest, and will provide a rationale for, is for members to take this enzymatically modified rice bran for only four months out of the year. (134)
We believe the substantial boost in natural killer cell activity will help eliminate virus-infected cells, premalignant cells, and senile cells that linger in the body and emit constant streams of pro-inflammatory cytokines. An underlying cause of aging is the accumulation of senile (senescent) cells that fail to undergo apoptosis (natural cell cycle destruction). (135) An increase in natural killer (NK) activity can help purge the body of these unwanted senescent cells. You're also going to learn in this issue of Life Extension magazine why removing cells infected with the CMV (cytomegalovirus) can result in a meaningful extension of the healthy human life span.
To further restore a more youthful immune profile, we're recommending that members go on a 60-day course of an over-the-counter drug called cimetidine.
This can be purchased at pharmacies at very low cost. We suggest that most people take 800 mg of cimetidine each night for 60 consecutive days to reduce excess regulatory T-cell counts and increase T-helper cell counts. Regulatory T-cells sometimes turn off the immune system before immune eradication of virus-infected cells and tumor cells occurs.
We think this 60-day cycle of cimetidine should be considered a few times during the year, but do not take it all the time. We don't have the data yet to support everyday use of cimetidine in protecting against immune senescence, but there is compelling evidence for shorter-term use. (136) Cimetidine is approved by the FDA for use in heartburn sufferers (The brand name of this drug is Tagamet[R].)
A trial was done on colorectal cancer patients who used 800 mg a day of cimetidine for one year. In these patients, cimetidine demonstrated significant survival benefits--84.6% of the cimetidine/ fluorouracil group were alive after 10 years compared to only 49.8% of the control group (given fluorouracil alone). (137)
Life Extension has recommended cimetidine to certain cancer patients since 1985, and the most robust benefits have been shown to occur when cimetidine is administered prior to surgery and other immunosuppressive cancer therapies. (138-142)
We urge members to get on a 60-day cycle of cimetidine now to bolster defenses against immune senescence and winter infections.
On page 33 of this issue is a listing of cimetidine side effects and contraindications.
We're On The Verge Of Something Big ...
In case you have not figured it out yet, we are entering a new paradigm in the prevention and reversal of age-related disease.
While certain nutrients Life Extension members have taken for decades help protect against immune decline, never before have we had such an arsenal to counteract the multiple underlying factors that characterize immune senescence. And this is just the beginning.
We are funding aggressive clinical research involving bone marrow rejuvenation with the objective of mobilizing hematopoietic stem and progenitor cells (HSPCs) that will rejuvenate every tissue of our aging bodies.
We are going even further in helping the very elderly with a research project that involves taking stem cell-stimulated blood of individuals under age 25, tissue-type matching it to elderly individuals, separating the youth factors from this young blood, and transfusing it into the elderly subjects. The objective of this research project is nothing short of meaningful age reversal in individuals who may have only a few more months or years to live.
How is this expensive research funded? By the dietary supplements you purchase from the Life Extension Buyers Club. We use proceeds from supplement sales to fund a wide range of projects aimed at finding cures for cancer, vascular disease, aging, and death itself. A record number of media stories this year highlighted areas of research we pioneered that are now being studied at prestigious universities.
Obtain Latest Formulations At Discount Prices
Once a year, we discount the price of every one of our advanced nutritional formulas. Members take advantage of this once-a-year Super Sale to stock up on their favorite supplement formulas.
What should comfort members more than anything else are the three novel methods to counteract aging we have introduced over the past few months. In addition to the immune senescence reversal program discussed in this editorial, there is now a supplement that mimics several of the longevity properties of the drug metformin, and a cell-regenerating nutrient called nicotinamide riboside that we've been working on since the year 2001.
We've also combined some nutrients into existing formulas so that members can obtain more benefits while swallowing fewer pills.
No organization in the world is combatting senescence and human mortality more aggressively than Life Extension. Your support via supplement purchases and donations enables us to expand on an unprecedented biomedical research endeavor.
To order nutrients you need today at Super Sale prices, call 1-800-544-4440.
For longer life,
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RELATED ARTICLE: Hidden Effects Of Natural Killer (NK) Cell Senescence.
Natural killer (NK) cells are best known for their impact on reducing the incidence and severity of viral infections. (28,31)
Overlooked are studies showing vibrant NK function is crucial for the immune system to recognize and eliminate unhealthy/ infected cells and dysfunctional (senile) cells.27115 A pathologic consequence of too many senile cells is tissue/organ damage and chronic inflammation. (116,119)
Senile (senescent) cells reside in a state of irreversible cellular paralysis. Your body wants them to die and disappear, but they linger on for dangerously long periods. While these senile cells contribute nothing to healthy function, they remain metabolically active, secreting an array of dangerous growth factors and pro-inflammatory cytokines.
Functional NK cells can eliminate senile cells before they buildup to lethal levels. When NK cells are hampered by aging, however, they are less able to remove deadly senile cells from our bodies.
As NK cells themselves become senescent in older people, there is increased reactivation of tuberculosis and viral illnesses (such as shingles and CMV), slow resolution of inflammatory responses, and increased incidence of bacterial/fungal infections and malignancies. (27,120)
It is likely that the senescence of NK cells has wider implications on the health of older adults than originally thought. NK cell senescence thus represents a dagger of vulnerability that predisposes us to premature suffering and death. It must be reversed to avert degenerative disease.
RELATED ARTICLE: Most People Don't Get Enough Zinc.
Immune cells are produced in the bone marrow and programmed into functional T-cellS by our thymus gland. Profound shrinkage (atrophy) of the thymus gland occurs with aging and in the presence of nutrient deficiency-especially zinc. (121,122)
Zinc supplementation in old animals stimulates thymus gland growth and increases youthful thymic functions critical to healthy immune regulation. (123,124)
In older adult humans, zinc deficiency is rampant. One reason for this is that the government's minimum recommended daily allowance for zinc is only 8 to 11 mg. (125) Yet 35 to 45% of people over age 60 don't even get half of that. (126,127)
Optimal levels of supplemental zinc is around 30 to 50 mg a day, so it is easy to see why even people taking basic RDA-potency vitamins are woefully short of this critical mineral.
Scientists now believe that zinc deficiency plays a direct role in the aging of the immune system. (128,129) The hormone DHEA is also important in maintaining youthful thymic function.
Zinc and DHEA are remarkably low-cost dietary supplements, and the fact that most people are deficient in one or both of them helps explain the epidemic of degenerative disease that occurs as human's age past 60 years, which is when immune senescence significantly manifests. As you've been reading, however, more than just zinc and DHEA are needed to ward off immune senescence.
RELATED ARTICLE: Premature Death Of Jack LaLanne Likely Caused By Immune Senescence.
It is impossible to overstate the magnitude of disability and death that immune senescence inflicts on aging human populations. When you hear a person died from "old age," in almost every instance the underlying culprit is a dysfunctional immune system that ignites deadly inflammatory fires while failing to protect against infections and malignancies.
No one we know tried to live for over 100 years more than health pioneer Jack LaLanne. He engaged in rigorous lifelong exercise and ate a low-calorie healthy diet. He followed an old-line supplement program probably devoid of vitamin K and DHEA, which may have contributed to his premature death at age 96.
Jack LaLanne died of pneumonia following aortic valve surgery. Aortic valve stenosis is caused by calcification, chronic inflammation, and other factors such as elevated homocysteine. (143)
Vitamin K prevents calcification that is so often the reason why an elderly person's aortic valve fails. (144,149) DHEA partially protects against inflammation. (150,152)
Immune senescence may very well have contributed to Jack LaLanne's early demise by crippling his ability to fight off the pneumonia, which was the acute cause of his death.
It is difficult to imagine someone as fit and vigorous as Jack LaLanne succumbing to pneumonia. Yet a dysfunctional immune system deprives even the hardiest of us from warding off infections that were easily overcome in our youth.
Clearly, protecting against immune senescence is a mandatory component of a longevity program.
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