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Scientist studying plant-based apigenin for removing senescent cells

Suppress Toxic Senescent Cell Secretions

Senescent cell accumulation is a contributor to systemic aging. Natural plant extracts can help reduce the senescent cell burden and lower the harmful compounds they emit.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, on June 2020. Written By Jason Fitzgerald.

When aged cells lose healthy functionality they’re supposed to die off and their remnants expunged from the body.

Senescent cells do not follow this rule.

They instead linger in a highly activated (toxic) state that damages healthy cells.

Cellular senescence is a major contributor to degenerative disorders and systemic aging.1-8

Senescent cells can be partially removed from the body using compounds known as senolytics.

Researchers have made another advance in senolytic strategy. They’ve identified that apigenin (a plant extract) reduces harmful compounds that senescent cells emit.

Senolytics Remove Senescent Cells

Scientists looking at a petri dish

A few years ago, researchers at the Mayo Clinic showed that it was possible to selectively remove senescent cells using drugs and other compounds known as senolytics.9

Initial studies relied on synthetic anti-cancer drugs as part of the senolytic regimen. Navitoclax and dasatinib are two cancer drugs that have been successfully used to eliminate senescent cells.10,11

One of the most studied senolytic treatments combines dasatinib with a nutrient found in many fruits and vegetables called quercetin. Each compound targets senescent cells in different ways.

In cell culture and animal studies, senolytics remove senescent cells and reduce disease, leading to longer lives for the animals.8,9,12-14

Last year a study confirmed that senolytics can eliminate senescent cells in human subjects!15

In this trial, a daily dose of 100 mg of dasatinib and 1,000 mg of quercetin for three days resulted in a significant reduction in senescent cells.

The results were seen in fat tissue, opening the door to potential senolytic treatments for those suffering from obesity, metabolic disease, and more.

What you need to know

A New Senolytic Triple Therapy

  • As cells age, some of them become senescent. This means they are dysfunctional, but don’t die off like most damaged cells.
  • Senescent cells rob their tissues of function. They also secrete compounds that incite chronic inflammation, causing damage and dysfunction to surrounding tissues.
  • Cellular senescence is linked to rapid aging and increased risk for chronic disease.
  • Senolytics are compounds capable of removing senescent cells. The most common senolytic therapy studied so far is a combination of the plant nutrient quercetin and a cancer drug, dasatinib.
  • Recent research has found that theaflavins from black tea provide similar senolytic effects as dasatinib.
  • A third nutrient, called apigenin, provides further protection. It suppresses the secretion of pro-inflammatory compounds by existing senescent cells.
  • Together, these three plant-based nutrients provide powerful protection against the damage done by cellular senescence.

Plant-Based Senolytics

Using cancer drugs even in very low doses concerns many natural-health enthusiasts.

Scientists have been searching for senolytic agents that do not rely on these drugs. They’ve recently made discoveries showing functional efficacy of plant-based senolytics.

In late 2019, a study was published indicating that the nutrient quercetin is successful as a senolytic agenton its own, without combining it with the cancer drug dasatinib.16

In this study, quercetin removed senescent cells in the kidneys of mice. This led to improved function and a decrease in the fibrosis (scarring) that causes deterioration and kidney failure.

Quercetin has also been shown to inhibit the proteins that block apoptosis, or programmed cell death, in senescent cells. This makes it easier for other senolytic compounds to eliminate damaged cells from tissues.17

The data still show that combining quercetin with dasatinib works better than quercetin alone. This led to a search for a plant-based compound that acts like dasatinib, without the side effects.

Scientists have discovered that theaflavins from black tea may act as a senolytic agent by inhibiting cellular receptors Eph, BRC-ABL, and BLC-218-21 to clear senescent cells from the body.

Increased activity by a signaling protein called ephrin has been linked to senescence, and dasatinib works in part by stopping ephrin (Eph) receptors from activating.9

Theaflavins block ephrin receptor activation and can prevent cell senescence.18,22

Research shows that theaflavins also inhibit BCL-2 proteins that make it easier to induce death in senescent cells. 21

Toxic Secretions Emitted by Senescent Cells

microscope with slide

Researchers realized that it’s not enough just to remove senescent cells from the body.

When cells become senescent, they don’t just sit there, as if inert. They undergo a series of transformations that result in their secreting high levels of toxic compounds collectively referred to as SASP or senescence-associated secretory phenotype.

SASP consists of protein-degrading enzymes that damage and destroy surrounding healthy cells and initiate chronic inflammation.23

This low-level inflammation silently damages tissues and organs, leading to disease, dysfunction, and accelerated aging.24

Persistent inflammation also contributes to weight gain and obesity, which increases risk for type II diabetes and metabolic syndrome, along with cardiovascular disease, cancer, and dementia.1-4,8,23-28

Los Angeles Times Reports on Senolytics

“This drug cocktail reduced signs of age-related diseases and extended life in mice and human cells”

“…A group led by Mayo Clinic anti-aging researcher James Kirkland not only offers a clear look at the power of senescent cells to drive the aging process, but also a pharmaceutical cocktail that, in mice at least, can slow and even reverse it…”

“Compared with mice that aged normally, those that started the dasatinib-quercetin cocktail at an age equivalent to 75 to 90 years in humans ended up living roughly 36% longer, and with better physical function …”

“Aging…is beginning to look more and more like a disease— and a treatable one at that.” — L.A. Times, July 10, 2018.

Why Senescent Cell Removal is not Enough

recreation of red blood cells in artery

It is not yet possible to remove all senescent cells that accumulate in our aging bodies. The best we can do is reduce what’s known as the “senescent cell burden.

Remaining senescent cells continue secreting SASP that slowly destroys healthy surrounding tissues by degrading proteins and igniting inflammatory fires.

To put this into perspective, Mayo Clinic scientists calculated that if only one in 7,000 to15,000 cells is senescent, then age-related problems in physical function started to appear in mice.

To protect against the senescent cell burden, more needs to be done to reduce the emission of toxic SASP.

A Triple-Action Senolytic Approach

Apigenin is a flavonoid found in certain herbs, fruits, and vegetables.

In two recent studies, apigenin was found to inhibit the SASP. This resulted in a reduction in pro-inflammatory compounds produced by senescent cells.29,30

Reducing inflammation caused by SASP while diminishing the senescent cell burden is crucial for healthy longevity.

Quercetin and theaflavins (from black tea) function via separate and complementary mechanisms to purge the body of senescent cells.

A strawberry flavonoid called fisetin may become one of the most effective senolytics, but it is not yet bioavailable enough to induce a systemic benefit.

A triple approach utilizing highly absorbable quercetin, theaflavins, and apigenin can attack cellular senescence from multiple angles, helping to rid the body of the damage it causes.

Enhancing Quercetin’s Effects

A challenge to fully benefiting from quercetin is that it can have low oral bioavailability.31

To improve quercetin’s absorbability so that the body can obtain higher benefits at lower doses, researchers integrated quercetin into a phytosome.

Phytosomes combine a natural compound (like quercetin) with a plant-based phospholipid carrier.32 This enables much more quercetin to enter the bloodstream to exert its beneficial effects throughout the body.

Summary

Scientists working in a laboratory

Cellular senescence is a major contributor to rapid aging and risk for degenerative illnesses.

Senolytic therapies remove senescent cells from the body, rejuvenating tissues and preventing the chronic damage that senescent cells do.

Major advances have been made in senolytic treatments in the last few years, including demonstrating that these interventions can remove senescent cells in human subjects.

Some of the earliest senolytic compounds used were chemotherapy drugs. Recent research has shown that plant-derived nutrients function via similar senolytic mechanisms.

Quercetin + theaflavins mimic senescent-cell-removing actions of quercetin and dasatinib (the cancer drug).

Apigenin provides added protection by reducing the emissions (SASPs) from residual senescent cells that ignite inflammatory reactions in our aging bodies.

As we await the development of bioavailable fisetin (a plant flavonoid), combinations of theaflavins, quercetin and apigenin are options for people over age 35-45 to consider.

Healthy younger individuals are unlikely to need senolytics as they have not yet acquired a toxic “senescent cell burden”.

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

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