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“We’re going after a cell type like antibiotics go after bacteria.”

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Grape-seed study reveals antioxidant compound may boost longevity

A new discovery, published in the journal 'Nature Metabolism,' suggests a key component of grape seeds called PCC1 can increase the health and lifespan of mice.

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As humans age, a cascade of physiological shifts occurs. Skin wrinkles, arteries and blood vessels stiffen, memory dulls, and bones lose density. On the whole, these changes mark the inevitable reality of old age and the health risks that come with it. But in a new, preliminary study, scientists reveal a powerful plant-based compound that may manipulate a root cause behind this physical decline: grape seed extract.

What’s new — The discovery, published Monday in the journal Nature Metabolism, suggests a key component of grape seeds, called PCC1, can increase the health and lifespan of mice by interfering with the work of certain harmful cells that promote disease.

Scientists are still far from harnessing this compound as a tool to help people, rather than animals, live longer and healthier lives. But the latest findings do represent a step forward in understanding the mechanisms that drive the aging process and manipulating them to our benefit.

Senolytics: What you need to know

Some age-related changes are visible to the eye, but others take place deep within the body’s complex cellular circuitry. One such hallmark of aging is a process called cellular senescence.

Cellular senescence goes like this: Throughout life, disease, stress, and injury can damage cells. Typically, the immune system is adept at clearing dysfunctional cells through a process called apoptosis. But sometimes, cell senescence arises — typically in old age. Damaged and dysfunctional cells accumulate, cause inflammation, and contribute to a range of age-related illnesses.

Originally discovered by Leonard Hayflick and Paul Moorhead in the 1960s, senescent cells have been linked to a long list of age-related conditions, including cancer, diabetes, osteoporosis, heart disease, stroke, Alzheimer’s disease, dementia, and osteoarthritis.

These diseases often occur “in synchrony,” as multimorbidities, Yu Sun, a co-author of the new study and a scientist at the Chinese Academy of Sciences, explains to Inverse.

“Aging is generally accepted as the single largest risk factor for most major chronic disorders,” Sun says.

What we don’t want to do is increase lifespan at all costs.”

While we possess a growing arsenal of drugs to treat many of these diseases independently, the combined effect of these pharmaceutical drugs on reducing illness and early death has been limited, or at least modest, Sun adds.

Enter a new class of drugs called senolytics, which aim to influence cellular senescence in an attempt to stave off multiple conditions, simultaneously. Instead of treating specific disorders one at a time, senolytics kill off bad cellular actors to keep multiple diseases at bay.

James Kirkland, a study co-author, gerontologist, and scientist at The Mayo Clinic, is a pioneer in the search for effective senolytics. Kirkland explains that it appears cellular senescence is a fundamental aging process.

“By targeting fundamental aging processes, we may be able to delay, prevent or alleviate the vast bulk of diseases and disorders that account for most morbidity, mortality, and health expenditures,” Kirkland tells Inverse.

Early trials of senolytics suggest they can decrease senescent cells, reduce inflammation and alleviate frailty in people. Dozens of clinical trials including animals and people with diabetes, Alzheimer's disease, osteoarthritis, and Covid-19 are underway to determine how senolytics might affect disease progression.

“This is no longer a one drug, one target, one disease approach,” Kirkland says. “We’re going after a cell type, much like antibiotics go after bacteria.”

It’s a hit-and-run strategy because once they’re gone, they’re gone, Kirkland says.

How they did it — To narrow down therapies that may target cellular senescence, the researchers scanned 46 plant extracts and compared their anti-aging capacities. The team screened each natural compound, also called a flavonoid, using a model involving cultured human prostate cells.

In these initial tests, one plant-based compound showed “outstanding potential,” Sun says: grape seed extract. Specifically, one of its key components is called procyanidin C1 (PCC1). In the human prostate cells, PCC1 appeared to selectively kill potentially harmful senescent cells while leaving normal cells intact.

The scientists studied PCC1’s effect on living animals. Specifically, researchers exposed mice to radiation and tested PCC1’s effect on resulting senescent cells. In these experiments, PCC1 injections reduced the number of senescent cells and led to health improvements in the mice.

To better understand PCC1’s effect on longevity, the research team rounded up 91 old mice. The group included 48 males and 43 females, which were 24 to 27 months old — a range equivalent to a human age of 75 to 90 years.

Every two weeks, they injected this group with PCC1. This therapy increased the mice’s remaining lifespan by over 60 percent and increased their total lifespan by approximately 9 percent.

Why it matters — Taken together, these findings suggest grape seed extract may be an effective senolytic with anti-aging and anti-cancer effects — at least in mice. Sun suggests that intermittent administration of PCC1 from grape seeds can significantly reduce the number of senescent cells in multiple tissue and organ types, and leads to health improvements.

“People should not be taking these things over-the-counter and physicians should not be prescribing them.”

Grape seeds are an advantageous therapeutic option — they are relatively cheap and accessible sources of healthy micronutrients.

“For years, people have been using grape seed extract as a regular agent of antioxidant, anti-inflammatory, or anti-cancer effects to improve their health conditions,” Sun says. But people did not know much about its anti-aging efficacy, he adds. Now, scientists have a clearer sense of these compounds’ effects in combating aging.

What’s next — Although grape seed extract shows promise in hampering a fundamental aging mechanism, it’s still too early to say people should incorporate the substance into their day-to-day lives. Sun cautions that human clinical trials are “necessary and warranted” to determine if and how much grape seed extract has meaningful anti-aging or anti-cancer benefits. Kirkland echoes that caution:

“Anything that sounds too good to be true, is,” Kirkland says. “People should not be taking these things over-the-counter and physicians should not be prescribing them.”

For now, consuming moderate amounts of grapes or grapeseed oil won’t likely hurt — and may offer a crucial antioxidant and anti-inflammatory boost. Future studies will determine whether doing so will extend life, however — and whether it is ultimately beneficial.

What we don’t want to do is increase lifespan at all costs,” Kirkland says. “We don’t want people to be 120 and feel like they are 120. We’ve got to improve healthspan so that people just don’t wake up one morning. You know, they play golf or go riding or jogging and then just one day, don’t wake up.

Abstract: Ageing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP). Here we show that procyanidin C1 (PCC1), a polyphenolic component of grape seed extract (GSE), increases the healthspan and lifespan of mice through its action on senescent cells. By screening a library of natural products, we find that GSE, and PCC1 as one of its active components, have specific effects on senescent cells. At low concentrations, PCC1 appears to inhibit SASP formation, whereas it selectively kills senescent cells at higher concentrations, possibly by promoting production of reactive oxygen species and mitochondrial dysfunction. In rodent models, PCC1 depletes senescent cells in a treatment-damaged tumour microenvironment and enhances therapeutic efficacy when co-administered with chemotherapy. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival. We identify PCC1 as a natural senotherapeutic agent with in vivo activity and high potential for further development as a clinical inter- vention to delay, alleviate or prevent age-related pathologies.

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