Grape Seed Extract Is a Potent Natural Defense Against a Hallmark of Aging By Killing Senescent Cells

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Story at a glance…

  • Grape seed extract kills senescent cells, a major driver of aging and its diseases.

  • Mice given grape seed extract lived longer, and mice of all ages performed better physically.

  • Grape seed extract is sold commercially, and doses up to 2,500 mg have been shown to be well-tolerated and generally safe.

Scientists studying natural compounds to neutralize senescent cells, zombie-like cells that drive inflammation, have demonstrated grape seed extract causes them to self-destruct while leaving normal cells unharmed.

This selective targeting is both rare and deeply sought after by scientists looking for pharmaceutical options to combat age-related morbidity. Driving home their previous observations in isolated cell cultures, applying 20 milligrams per kg of body weight of a flavonoid inside grape seed extract called PCC1 to aged mice, the scientists were able to restore youthful muscle function in a variety of strength and endurance tests, as well as extend overall lifespan.

The mice were equivalent to the ages of 75-90 in humans, and the dose of PCC1 from grape seed extract increased their remaining lifespan by over 60% or increased their total lifespan by approximately 9%.

Senescent cells, which grape seed extract was thought to potentially diminish, are one of the nine hallmarks of aging. They are neither living nor dead, neither function normally, nor directly attack our bodies, but are rather stuck in a kind of cellular purgatory following mechanisms within the cell deactivating its ability to divide; normally following exposure to chemicals or ionizing radiation.

“Transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues,” write the authors of a July 2018 paper on the topic. “Transplanting even fewer senescent cells had the same effect in older recipients and was accompanied by reduced survival, indicating the potency of senescent cells in shortening health- and lifespan”.

In this recent study, Yu Sun and colleagues treated mice which, had just received transplants of senescent cells, with PCC1 and found increased maximal walking speed, grip strength, and hanging endurance. Dramatically, the effect of one week of treatment was detectable two weeks after exposure to the senescent cells, and remained detectable for months after.

PICTURED: The Nine Hallmarks of Aging, in which DNA damage sustained through life cause the systems of intracellular communication to become obscured, as well as the abilities to repair tissues.

Precision apoptosis

But why exactly are senescent cells so damaging? In their state of purgatory, they continuously release a soup of pro-inflammatory molecules called senescence-associated secretory phenotype (or SASP) which inflames surrounding tissues and causes dysfunction therein.

“The list of age-related diseases definitively linked to cellular senescence keeps growing, as does the number of biotech companies racing to develop drugs to eliminate senescent cells,” said Buck Institute for Aging professor Judith Campisi, Ph.D., in a study reported on by WaL earlier this year.

Grape seed extract can treat senescent cells by unleashing the powerful PCC1 upon their mitochondria. Treatment in vitro of senescent cells with the maximum dose of PCC1 killed 90% of them while even after doubling the maximum dose, normal healthy cells were totally unaffected.

In vitro tests were conducted on a variety of cells, including various fibroblasts, endothelial cells, and stem cells. In all cases, the senescent cells were cleared by the activation of apoptosis, the primary cellular cleanup and repair process in humans. To double-check, the researchers used an apoptosis-blocking compound, and sure enough, PCC1 lost its senolytic touch, and the zombie cells survived.

Additional tests were done and found that PCC1 promoted the regression of tumors, the lowering of resistance to chemotherapy drugs in the tumor microenvironment, and previous research has also shown that procyanidins like PCC1 can chelate metals (the scientific term for “detox”), scavenge free-radicals, prevent the production of reactive oxygen species, and reduce hyperperoxide formation. Quite the resume.

Grape seed extract supplementation

What then, can we garner from this research to use in our day-to-day lives? Plenty of research has been done on grape seed extract, though much of it in the animal feed industry. The seeds themselves make up between 38-52% of the dry weight of the fruit, and PCC1, the agent responsible for clearing senescent cells, is called a procyanidin, which belongs to the flavonoid class of polyphenols.

Procyanidin is a kind of proanthocyanidin. The latter is marketed in grape seed extract supplements as “OPC” or oligomeric proanthocyanidin, and will generally have its own milligram measurements: for example 1,000 milligrams of grape seed extract, and 150 milligrams of OPC.

It was already at the turn of this century that consumers began to turn to grape seed extract as a health supplement. Sun et al. used 20 milligrams per kilogram of body weight in their mouse exercise model, which amounts, for example, to 1,600 milligrams of PCC1 for a 180-pound man, or 1,200 milligrams for a 130-pound woman.

Most of us won’t be able to get synthesized PCC1 from a lab, and if consumers want to go on the supplement market, at the moment they must settle for the OPC metric. Some supplements will have much higher concentrations of OPC than others. Some will combine grape seed extract with resveratrol, another anti-aging and anti-inflammatory supplement, but resveratrol has its own dose-dependent metrics and particulars.

Although PCC1 injections appear to have been well tolerated in mice in preclinical trials, research is needed, the authors stress, to establish what constitutes a safe dose and whether these findings are applicable to humans.

One study of 29 healthy Japanese participants showed that doses of 1,000, 1,500, and 2,500 milligrams of proanthocyanidin-rich grape seed extract taken orally were generally safe and well-tolerated in humans.

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2 thoughts on “Grape Seed Extract Is a Potent Natural Defense Against a Hallmark of Aging By Killing Senescent Cells

  1. I wonder what the difference is between injecting PCC1, like in the mouse study, and taking it orally? If GSE has been used for other things in the past, maybe people know how much of it is absorbed in the gut, and its bioavailability, where does it go in the body? Does it cross the blood brain barrier? Does it get broken down into other chemicals or used in any way? What is the half life in the blood? How quickly is it excreted? All these things are more or less known for fisetin, and probably for GSE as well, but not by people studying senolytics. GSE is available in different grades, 50:1 extraction ratio, 20:1 etc. It would be nice to know how much PCC1 is in them. Finally, we need to study how GSE works in combination with other senolytics like fisetin and quercetin. I tried GSE with Fisetin and didn’t notice any ill effects. But I’m not testing myself, and don’t have a measure of how effective the treatments are.

  2. Other derivatives from grapes, such as resveratrol and quercetin are generally well-tolerated, even into measurements of grams. We are very eager to see more research done in this field, and will certainly continue to publish on it.

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