Sweep Away Senile Cells
By Christopher Wilson
If someone told you that taking a certain nutrient or drug could kill some of your cells, you might think it was a bad idea.
What few people understand is that as cells age, some of them degenerate into a population of poorly functioning senescent cells that accumulate throughout their body.1,2
There is no value to retaining these lingering senile cells. Their continued presence underlies a myriad of degenerative disorders. Senescent cells should be purged from the body!
The buildup of these dysfunctional senile cells contributes to decay of individual organs and greater susceptibility to disorders related to chronic inflammation.3,4
Pharmaceutical companies are developing technologies to remove or neutralize senile cells. They view this as a lucrative target of anti-aging research.6,7 The objective is to selectively remove senescent cells without damaging healthy cells.
Rather than wait for expensive drugs, scientists have discovered that the plant flavonoid quercetin has the unique ability to selectively remove old cells without harm to normal, actively dividing cells.8 This has the obvious potential for extending health span.
A number of studies suggest that low-cost quercetin may slow aging and reduce the risk of many age-accelerating processes—both by clearing senescent cells and via other beneficial mechanisms.9,10
Aging Cells, Aging Organs, Aging Body
It might seem logical that our cells age at the same time as our body as a whole, but that is not the case.
Cells have varying life spans. Some cells live only briefly and replace themselves frequently, while others have longer life spans and are replaced only after weeks, months, or even years.11,12 The exact frequency of cell renewal depends on the tissue in which the cells are found.
In the presence of various detrimental stimuli (such as ultraviolet radiation, oxidation, and environmental toxins), some cells undergo changes to their DNA that results in old cells that won’t die when they’re supposed to.13,14 Scientists refer to these as senescent (senile) cells.
Senescent cells pose a significant health problem because many of them produce pro-inflammatory signaling molecules and protein-digesting enzymes that contribute to acceleration of age-related diseases.7,15
A healthy immune system can help remove senescent cells as part of its normal cellular housekeeping. This process is important in cancer prevention.7,16 As bodies age, the immune system itself begins to age via a process known as immune senescence. As a result, removal of senescent cells begins to fail. This leads to an acceleration of aging, and ultimately, an increase in the risk of most age-associated conditions, including cancer.16
By selectively eliminating senescent cells so that they do not “clog up” our body’s processes, it is possible to support or even regain youthful function in every organ and tissue. This was shown in a compelling fashion in a 2011 study from the Mayo Clinic, using a mouse model of rapidly accelerated aging similar to the disease progeria in humans.17
Progeria is a rare disease of accelerated aging. It is the result of a gene mutation that produces premature accumulation of senescent cells, and causes young children to age so rapidly that most die before age 15, commonly of atherosclerosis or other age-related processes.18,19
The Mayo researchers transplanted into the rapidly aging mouse model a specialized gene that selectively eliminated senescent cells.17 They found that, by removing senescent cells in tissues such as fat, skeletal muscles, and the eye, they could significantly delay onset of age-related disorders in those tissues. These included muscle loss, cataracts, and depletion of subcutaneous (under-the-skin) fat. Perhaps still more exciting, clearance of senescent cells even in late life slowed the progression of age-related disorders already in progress.
This study opened the door to the idea of senolytic (or “age-busting”) drugs. Testing this kind of gene transplantation therapy in humans is fraught with risks. A better, safer, and simpler solution was discovered in early 2015 by another group of scientists from several institutions, including the Mayo Clinic.8
Delete Senescent Cells with Quercetin
The second Mayo study was carried out by researchers who recognized the threat of senescent cell accumulation. These scientists sought to correct this pathology in a simpler and safer way than gene transfers. They knew, from past research, that clearing away just 30% of senescent cells produced profound improvement in age-related signs and symptoms.8
The researchers turned to several compounds known to induce cellular suicide (known technically as apoptosis) preferentially in senescent cells, while leaving healthy cells untouched. They tested 46 different drugs and nutrients, and ended up with two candidates: a chemotherapy drug called dasatinib and quercetin, a well-studied nutrient found naturally in apples, onions, and other vegetables.20 Both compounds powerfully affect the cellular regulation systems that produce beneficial apoptosis, but dasatinib, unlike quercetin, has a wide range of serious toxic side effects.21-24
When human cell cultures were treated with either quercetin or dasatinib, the researchers found a sharp reduction in numbers of senescent cells. In this study, quercetin caused about a 50% reduction at the lowest two doses, with no effect on healthy cells.8 Dasatinib had similar effects when used alone.
In an animal study, the combination of the two compounds was still more effective. When administered to age-accelerated mice, the combination caused a significant reduction in a score of age-related symptoms, including hunched back, poor muscle function, tremors, loss of grip strength, gait abnormalities, urinary incontinence, and poor body condition. These effects were interpreted as an extension of the health span of the mice, both because of the delay in symptom onset and the reduction of their severity.8
Of course, no one is proposing that dasatinib, a powerful chemotherapy drug, be used to prevent human aging. This study shows that quercetin alone is just as effective at deleting dangerous senescent cells as the drug dasatinib, and that such deletion delays aging and promotes a longer health span.8
Like most natural supplements, quercetin appears to achieve its effects by multiple pathways. For example, quercetin activates a well-researched enzyme known as SIRT1, which is also activated by resveratrol.25 Recent studies show that activated SIRT1 can suppress the pro-inflammatory signaling of senescent cells, thereby reducing their toxicity and potentially slowing aging.26 Numerous experiments have demonstrated that animals with experimentally increased SIRT1 activation live longer and experience fewer age-related disorders.27,28
Previous animal studies have shown that quercetin can extend life span. In one often-used model of aging using the roundworm Caenorhabditis elegans, quercetin treatment has been shown to prolong the mean life span by 16 to 23%.29-32
A wealth of evidence shows that quercetin acts by several mechanisms to delay aging, is safe, and is absorbed from the gastrointestinal tract after an oral dose.33,34 It is reasonable to examine quercetin’s effects as an age-decelerator in the human tissues most affected by aging, as we’ll now see.
Quercetin Slows Cardiovascular Aging
Cardiovascular disease (heart attacks, congestive heart failure, and stroke) is the leading cause of death among older Americans.35 Finding a way to slow aging of the heart and blood vessels is a vital factor when seeking to significantly prolong human life. Quercetin has numerous properties that help to combat various factors involved in heart disease.
First, quercetin has the ability to relax blood vessels, an action that reduces the risk of heart attack and stroke.36 Scientists believe this is due in part to quercetin’s ability to fight oxidation. Oxidation in cells that line blood vessels reduces their ability to produce and respond to nitric oxide, a vital signaling molecule that helps control blood pressure by telling cells to dilate and relax.
Secondly, quercetin has been found to increase levels of an important enzyme called paraoxonase-2 (PON2).34 Scientists now believe that this potent enzyme protects fat molecules from dangerous oxidation that can lead to atherosclerotic plaque formation and decreased blood flow.34 Indeed, animal studies demonstrate that supplementation withquercetin reduces markers of oxidation, while increasing heart weight (an indicator of good function in healthy animals), potentially improving the animals’ long-term health.37
The third way quercetin helps protect against heart disease is by counteracting the pro-clotting effect of platelets, a leading contributor to arterial blockage in the presence of plaque. In a study of healthy human volunteers, doses of a quercetin supplement at both 150 and300 mg were shown to decrease the clotting of platelets. This action has the potential to reduce the risk of stroke and heart attacks.20
Finally, quercetin directly opposes major components of metabolic syndrome (the combination of obesity, hypertension, glucose intolerance, insulin resistance, and lipid disturbances), a condition that vastly increases cardiovascular risk. When a group of overweight or obese subjects with features of metabolic syndrome received a daily 150 mg dose of quercetin for six weeks, mean fasting quercetin blood levels were boosted by nearly 4-fold.38 In this study, quercetin lowered systolic (top number) blood pressure and reduced levels of oxidized LDL (bad) cholesterol, a contributor to atherosclerosis.
Another study evaluated healthy men who had a genetic variant that increases cardiovascular risk. A quercetin dose of 150 mg per day was used. After eight weeks, there were reductions in waist circumference, after-meal systolic blood pressure, and triglyceride levels. Beneficial increases in HDL (good) cholesterol were found in these men taking just 150 mg per day of quercetin.36
Quercetin Protects Brain Cells
Scientists have determined that senescent, inflammation-generating cells accumulate in the brain during “normal” aging. This discovery has opened a new door to therapies aimed at preventing the decline associated with neurodegenerative diseases like Parkinson’s and Alzheimer’s. With quercetin’s ability to selectively delete senile cells in the brain, we can expect further advances in preventive neurology from this impressive natural flavonoid.
A great deal has already been discovered about quercetin’s ability to reduce the memory deficits and other features of neurodegenerative disorders by protecting brain cells’ structure and function.39
Studies show, for instance, that quercetin is absorbed in the blood after oral dosing, and is detectable soon thereafter in brain tissue.40 As a result, quercetin has been shown to help protect the brains of rats subjected to a high-stress environment.
In a study published in Free Radical Biology and Medicine, the rats initially developed oxidative stress in vital memory and movement centers of their brains as a result of the high-stress environment.40 However, when those same rats were supplemented with quercetin, the cognitive deficits they had experienced were reduced.
Oxidative stress and senescent cells are significant contributors to the gradual development of Alzheimer’s and Parkinson’s diseases, two common neurodegenerative consequences of aging.41-43 Quercetin has been shown to help battle both of these underlying issues.
In a rat model of Parkinson’s disease, quercetin or fish oil demonstrated valuable brain-protective properties. However, the combination of quercetin and fish oil produced even more protective benefits such as reducing behavioral impairment, improving production of the neurotransmitter dopamine, and rescuing ailing mitochondria.44
Protection Against Environmental Toxins
Environmental toxins play a significant role in the development of neurodegenerative diseases. Parkinson’s disease, for example, is known to be promoted by exposure to PCBs (polychlorinated biphenyls, a class of environmental chemical toxins).45,46 PCBs damage brain cells that produce the neurotransmitter dopamine, which is deficient in Parkinson’s disease.47-49 Brain dopamine levels steadily decline as humans age past 45 years.50
One study demonstrated that quercetin reduces damage to dopamine-producing brain cells after rats are exposed to PCBs.39 Subsequent experiments demonstrated that quercetin protected the dopamine-producing cells by scavenging the destructive oxygen-free radicals induced by the toxin.39
In addition to memory loss, animals exposed to PCB also developed signs of anxiety. A separate study found that quercetin supplementation was able to reverse both the brain changes and the neurological deficits associated with PCB-induced anxiety.51
Further supporting quercetin’s ability to protect the brain from damaging toxins, a study published in Toxicology and Industrial Health found that supplementation with the nutrient reversed changes in the brains of rats previously exposed to a common industrial solvent called toluene. When the researchers examined microscopic evidence of the animals’ brains, they found that quercetin supplementation in fact led to structural improvements in brain architecture that had been damaged by the chemical. Amazingly, these improvements occurred even when quercetin was administered after the brain damage was done.52
Exposure to PCB weakens the blood-brain barrier, which allows PCB and other damaging toxins to leak into brain cells.53 However, researchers found that quercetin can protect brain cells against environmental toxins by stopping them from ever reaching the brain in the first place.53
The accumulation of pro-inflammatory senescent cells in the maturing body is an underlying factor behind premature aging. Research into this scientific arena provides a real-world opportunity to combat this degenerative mechanism.
Quercetin is a flavonoid found in many fruits and vegetables. It has recently been shown to remove dysfunctional cells without harming healthy ones.
Studies in animals and humans show that quercetin fights oxidative stress and inflammation, while beneficially modulating genes known to be involved in the aging process.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
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