Life Extension Magazine October 2016
Natural Compounds that Remove Aging Cells
By Sherrie Oppenheimer
Scientists have recently been focused on a new class of drugs1 aimed at eliminating aging cells from our bodies.
The goal of these experimental drugs is to eliminate poorly functioning, senile cells that clog our bodies and induce a range of degenerative illnesses.
This form of biological housekeeping frees the body from sluggish, slowly dying cells and allows it to function better with newer, healthier cells. This rejuvenation occurs naturally in our youth but declines with age.
Researchers have discovered that two natural compounds target and discard aging cells from the body, making way for the production of new, healthy cells.
What you need to know
- The accumulation of non-replicating aging cells in healthy tissue promotes aging throughout the body.
- At the same time, cancer cells lose the ability to grow old and stop replicating, leaving them free to multiply endlessly, invading and destroying tissue as they go.
- Tocotrienols, members of the vitamin E family, have recently been shown to exert dualistic actions on healthy and malignant cells, stimulating natural growth and delaying senescence in otherwise healthy cells, but inducing senescence and stopping growth in malignant cells.
- These properties make tocotrienols among the most promising senolytic compounds that are readily available.
- Tocotrienols have also been shown to fight type II diabetes, and metabolic syndrome, while also delaying neurodegeneration.
Targeting Cellular Senescence
Cellular senescence is an underlying contributor to accelerated aging and disease.2
Aging, or “senile,” cells stop dividing to produce new cells and lose their ability to die off, which causes them to build up in the body. These accumulated cells pour out harmful, pro-inflammatory chemicals and other signaling molecules that contribute to aging and increase the risk of most age-related diseases—including cancer.3-5
Ridding the body of these aging cells to make way for fresh new cells is an important target for slowing aging and reducing disease risk.6 This is the goal of pharmaceutical researchers as they develop new drugs to purge senile cells from aging bodies.
But senescence is a double-edged sword. While it is harmful in healthy cells, senescence is desirable in tumor cells because it halts their out-of-control replication. By definition, cancer cells have become “immortal,” and continue to replicate without forming useful structures. By “turning back on” the senescence process, cancer cells can be made “mortal” again and eventually die off. In fact, deliberately triggering senescence in malignant cells represents a new approach to fighting cancer.6
The idea that we can use natural substances to selectively target cellular senescence has opened a promising new door in the fight against cancer and aging.6
Studies have used drugs and synthetic biological products capable of clearing away accumulated aging cells in aging tissues. In animals, these compounds have produced dramatic results, such as delaying the onset of aging, slowing existing age-related changes, and even extending lifespans.7-9 But in their current state of development, these drugs and other synthetic products are impractical, dangerous, or both, making them entirely unsuitable for use in humans to prevent either aging or cancer.
Researchers have found that two natural compounds, when combined, successfully remove aging cells from the body without harmful side effects.
Tocotrienols + Quercetin
Tocotrienols, the less well-known members of the vitamin E family, are emerging as the ideal senolytic nutrient. Studies show that tocotrienols have dual and complementary actions:
- In cancer cells, tocotrienols can stimulate cellular senescence, shutting down their malignant potential.6
- In healthy tissue, tocotrienols can slow aging changes, promote normal cell division and specialization, and prevent cells from reaching their damaging final aging state.10-14
Studies have shown the benefits of combining tocotrienols with quercetin, a flavonol found in many fruits and vegetables. Quercetin also has dual and complementary actions with regards to aging cells. Like tocotrienols, quercetin can induce senescence and promote cell death in numerous types of cancer cells.6,15 And, like tocotrienols, quercetin has the opposite effect in healthy cells, delaying senescence in younger cells and rejuvenating older cells to rid them of their abnormal, age-promoting function.1,6
Together, these two nutrients sweep the body clear of aging cells, while promoting natural termination of cancer cells.
Combined Anti-Aging Effects
Several studies have now been performed on the combination of tocotrienols and quercetin in slowing, delaying, or even reversing the consequences of senescence—particularly the excessive inflammatory signals that aging cells produce.16-18
A key reason why aging cells are so closely tied to aging and disease is because they pour out substances that generate inflammation throughout the body.3,19 In fact, aging cells are now recognized as an important source of the chronic inflammation that is known to produce age-related diseases.16
Growing evidence from animal models shows that the combination of tocotrienols plus quercetin sharply reduces blood levels of pro-inflammatory molecules.16 By suppressing these damaging factors, tocotrienols and quercetin reduce systemic inflammation in the body.17,18 Reducing inflammation has the beneficial effect of reducing the overall risk of aging and disease.
New Approach to Fighting Cancer
As we’ve seen, cancer cells are essentially “immortal” in part because they have lost the ability to enter senescence, and hence, to stop their out-of-control replication. That means that deliberately inducing senescence in cancer cells is a potentially effective method of slowing or stopping a tumor from continuing to grow—or even from developing in the first place.
Mounting evidence has demonstrated that treating malignant cells with tocotrienols has several anti-tumor effects, including:
- Inducing mitochondrial damage, which starves cancer cells of energy, and
- Inducing apoptosis, the normal cell death program that cancer cells lose.20-24
What is so remarkable is that these cell-damaging effects are not seen in healthy, non-malignant cells, which means that tocotrienols selectively target cancer cells.21
In addition to helping prevent the growth and development of tumors, it appears that tocotrienols could also play a role in preventing them from spreading to other parts of the body. Studies of cultured cells show that tocotrienols are intimately involved in the regulation of tumor cell invasion and metastases, through their intricate control of sign-aling pathways used by those cells.25
One specific member of the tocotrienol family, gamma tocotrienol, has its own list of actions against cancer cells. These include blocking the formation of new blood vessels (angiogenesis) that is required to feed fast-growing tumors, thereby starving them of their nutrient and oxygen sources,26,27 and inhibiting the production of the inflammatory molecules that are associated with aging cells and that promote cancer growth.28
Laboratory and preclinical studies suggest that tocotrienols may combat senescence-related deterioration. One in vitro experiment showed that tocotrienols may reverse premature aging of muscle cells by enhancing their regenerative capacity.29 Another cell study found that tocotrienols reversed senescence-associated cell cycle arrest, reduced DNA damage, and restored telomerase activity in human connective tissue cells.30 Several other lab studies have revealed similarly intriguing findings.6,31 In aged mice, tocotrienols increased mitochondrial function in the brain,32 and reduced the age-related decline in T-cell function.33
The ability of tocotrienols to slow the growth of cancer cells—as well as enhance their ability to die off naturally—has led to impressive results in animal studies of cancer.
One study showed that in mice that had been injected with human colon cancer cells, those being fed tocotrienol-rich plant oil demonstrated a significant inhibition of tumor growth.34
But what makes tocotrienols particularly unique is that while they induce senescence in cancer cells, they prevent aging changes in healthy tissues. This ability to selectively target cancer cells while protecting healthy cells was clearly seen in a study utilizing high doses of radiation.
Radiation therapy is often used in the treatment of malignant tissues, with the aim of destroying cancer cells. Unfortunately, this has the obvious side effect of producing radiation damage in healthy tissue as well, which can lead to premature cell senescence, dysfunction, and death—particularly in tissues with normally rapid cell turnover, such as the intestine. It can also lead to potentially life-threatening side effects and considerable misery.
But something remarkable happened when mice were supplemented with tocotrienols (human equivalent dose of
1 gram) prior to whole-body
radiation. Normal intestinal cells sharply increased their expression of life-preserving genes that prevent
cell death by apoptosis. In other words, while
tocotrienols are senescence-inducing in cancer cells, this experiment showed that
tocotrienol supplementation prevented radiation-induced aging changes in healthy
Several trials have shown benefits with daily doses of roughly 40–400 mg of tocotrienols in relation to lipid metabolism,36-44 brain health,42 liver health,43,44 immune system function,45 and prevention of damage to DNA.46
Tocotrienols, the less well-known members of the vitamin E family, are of great interest to researchers. Recent studies show that tocotrienols have the ability to slow cellular aging in normal tissues, while reducing inflammation. At the same time, in what seems to be a remarkable fashion, tocotrienols may accelerate the destruction of cancer cells.
Tocotrienols, particularly in combination with quercetin, appear capable of removing many aging cells.
Tocotrienols have other anti-aging effects that are proving beneficial in our fight against diabetes, metabolic syndrome, and neuro-degeneration.42,47-53
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
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- Chinta SJ, Woods G, Rane A, et al. Cellular senescence and the aging brain. Exp Gerontol. 2015;68:3-7.
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- Malavolta M, Pierpaoli E, Giacconi R, et al. Pleiotropic Effects of Tocotrienols and Quercetin on Cellular Senescence: Introducing the Perspective of Senolytic Effects of Phytochemicals. Curr Drug Targets. 2016;17(4):447-59.
- Baker DJ, Wijshake T, Tchkonia T, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479(7372):232-6.
- Xu M, Tchkonia T, Kirkland JL. Perspective: Targeting the JAK/STAT pathway to fight age-related dysfunction. Pharmacol Res. 2016;111:152-4.
- Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016;530(7589):184-9.
- Khor SC, Razak AM, Wan Ngah WZ, et al. The Tocotrienol-Rich Fraction Is Superior to Tocopherol in Promoting Myogenic Differentiation in the Prevention of Replicative Senescence of Myoblasts. PLoS One. 2016;11(2):e0149265.
- Khor SC, Mohd Yusof YA, Wan Ngah WZ, et al. Tocotrienol-rich fraction prevents cellular aging by modulating cell proliferation signaling pathways. Clin Ter. 2015;166(2):e81-90.
- Durani LW, Jaafar F, Tan JK, et al. Targeting genes in insulin-associated signalling pathway, DNA damage, cell proliferation and cell differentiation pathways by tocotrienol-rich fraction in preventing cellular senescence of human diploid fibroblasts. Clin Ter. 2015;166(6):e365-73.
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