In a new study, researchers found that a new drug based on a component of grape seed extract can successfully extend the lifespan and health of mice.
The study, published in the journal Nature Metabolism, lays the groundwork for further clinical studies to determine whether these effects can be replicated in humans.
Aging is a key risk factor for many chronic diseases. Scientists believe this is partly due to cellular aging. This occurs when cells can no longer perform their biological functions in the body.
In recent years, researchers have discovered a class of drugs called senolytics. These drugs can destroy senescent cells in laboratory and animal models, potentially reducing the incidence of chronic diseases that arise as we age and live longer.
In this study, scientists discovered a new senolytic derived from a component of grape seed extract called proanthocyanidin C1 (PCC1).
Based on previous data, PCC1 is expected to inhibit the action of senescent cells at low concentrations and selectively destroy senescent cells at higher concentrations.
In the first experiment, they exposed mice to sublethal doses of radiation to induce cellular senescence. One group of mice then received PCC1, and the other group received vehicle carrying PCC1.
The researchers found that after the mice were exposed to radiation, they developed abnormal physical characteristics, including large amounts of gray hair.
Treatment of mice with PCC1 significantly altered these characteristics. Mice given PCC1 also had fewer senescent cells and biomarkers associated with senescent cells.
Finally, the irradiated mice had less performance and muscle strength. However, the situation changed in mice given PCC1, and they had higher survival rates.
In the second experiment, the researchers injected aging mice with PCC1 or vehicle every two weeks for four months.
The team found large numbers of senescent cells in the kidneys, liver, lungs and prostates of old mice. However, treatment with PCC1 changed the situation.
Mice treated with PCC1 also showed improvements in grip strength, maximum walking speed, hanging endurance, treadmill endurance, daily activity level, and balance compared to mice that received vehicle alone.
In a third experiment, the researchers looked at very old mice to see how PCC1 affected their lifespan.
They found that mice treated with PCC1 lived an average of 9.4% longer than mice treated with vehicle.
Moreover, despite living longer, PCC1-treated mice did not exhibit any age-related higher morbidity compared with vehicle-treated mice.
Summing up the findings, corresponding author Professor Sun Yu from the Shanghai Institute of Nutrition and Health in China and colleagues said: “We hereby provide proof of principle that [PCC1] has the ability to significantly delay age-related dysfunction even when taken.” later in life, has great potential to reduce age-related diseases and improve health outcomes, thereby opening new avenues for future geriatric medicine to improve health and longevity.”
Dr James Brown, a member of the Aston Center for Healthy Aging in Birmingham, UK, told Medical News Today that the findings provide further evidence of the potential benefits of anti-aging drugs. Dr. Brown was not involved in the recent study.
“Senolytics are a new class of anti-aging compounds that are commonly found in nature. This study shows that PCC1, along with compounds such as quercetin and fisetin, is able to selectively kill senescent cells while allowing young, healthy cells to maintain good viability. ”
“This study, like other studies in this area, examined the effects of these compounds in rodents and other lower organisms, so much work remains before the anti-aging effects of these compounds in humans can be determined.”
“Senolytics certainly hold the promise of being the leading anti-aging drugs in development,” Dr. Brown said.
Professor Ilaria Bellantuono, professor of musculoskeletal aging at the University of Sheffield in the UK, agreed in an interview with MNT that the key question is whether these findings can be replicated in humans. Professor Bellantuono was also not involved in the study.
“This study adds to the body of evidence that targeting senescent cells with drugs that selectively kill them, called ‘senolytics,’ can improve body function as we age and make chemotherapy drugs more effective in cancer.”
“It’s important to note that all the data in this area comes from animal models—in this particular case, mouse models. The real challenge is to test whether these drugs are equally effective [in humans]. There are no data available at this time.” , and clinical trials are just beginning,” said Professor Bellantuono.
Dr David Clancy, from the Faculty of Biomedicine and Biological Sciences at Lancaster University in the UK, told MNT that dose levels could be an issue when applying the results to humans. Dr. Clancy was not involved in the recent study.
“The doses given to mice are often very large compared to what humans can tolerate. Appropriate doses of PCC1 in humans may cause toxicity. Studies in rats can be informative; their liver appears to metabolize drugs more like a human liver than a mouse liver. ”
Dr Richard Siow, director of aging research at King’s College London, also told MNT that non-human animal research may not necessarily lead to positive clinical effects in humans. Dr. Siow was also not involved in the study.
“I don’t always equate the discovery of rats, worms and flies with people, because the simple fact is that we have bank accounts and they don’t. We have wallets, but they don’t. We have other things in life. Emphasize that animals We do not have: food, communication, work, Zoom calls. I’m sure rats can be stressed in different ways, but usually we’re more concerned about our bank balance,” Dr. Xiao said.
“Of course, this is a joke, but for context, everything you read about mice cannot be translated to humans. If you were a mouse and wanted to live to be 200 years old – or the mouse equivalent. At 200 years old, that would be great, but does it make sense to people? That’s always a caveat when I talk about animal research.”
“On the positive side, this is a strong study that gives us strong evidence that even many of the pathways my own research focused on are important when we think about lifespan in general.”
“Whether it’s an animal model or a human model, there may be some specific molecular pathways that we need to look at in the context of human clinical trials with compounds like grape seed proanthocyanidins,” Dr. Siow said.
Dr. Xiao said one possibility is to develop grape seed extract as a dietary supplement.
“Having a good animal model with good results [and publication in a high-impact journal] really adds weight to the development and investment in human clinical research, whether from government, clinical trials or through investors and industry. Take over this challenge board and put grape seeds into tablets as a dietary supplement based on these articles.”
“The supplement I’m taking may not have been clinically tested, but animal data suggests it increases weight – which leads consumers to believe there’s something in it. It’s part of how people think about food.” additives.” in some ways, this is useful for understanding longevity,” Dr. Xiao said.
Dr. Xiao emphasized that a person’s quality of life is also important, not just how long they live.
“If we care about life expectancy and, more importantly, life expectancy, we need to define what life expectancy means. It’s okay if we live to be 150, but not so good if we spend the last 50 years in bed.”
“So instead of longevity, perhaps a better term would be health and longevity: you may well be adding years to your life, but are you adding years to your life? Or are these years meaningless? And mental health: you can live to be 130 years old. old, but if you can’t enjoy these years, is it worth it?”
“It’s important we look at the wider perspective of mental health and wellbeing, frailty, mobility problems, how we age in society – are there enough medications? Or do we need more social care? If we have support to live to 90 , 100 or 110? Does the government have a policy?”
“If these drugs are helping us, and we are over 100 years old, what can we do to improve our quality of life rather than just taking more drugs? Here you have grape seeds, pomegranates, etc.,” said Dr. Xiao. .
Professor Bellantuono said the results of the study would be particularly valuable for clinical trials involving cancer patients receiving chemotherapy.
“A common challenge with senolytics is determining who will benefit from them and how to measure benefit in clinical trials.”
“Additionally, because many drugs are most effective at preventing disease rather than treating it once diagnosed, clinical trials could take years depending on the circumstances and would be prohibitively expensive.”
“However, in this particular case, [the researchers] identified a group of patients who would benefit from it: cancer patients receiving chemotherapy. Moreover, it is known when the formation of senescent cells is induced (i.e. by chemotherapy) and when “This is a good example of a proof-of-concept study that can be done to test the effectiveness of senolytics in patients,” said Professor Bellantuono. ”
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