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''Zombie Cells” May Be Aging You


The average American begins to feel “old” at the age of 47. Oftentimes in our 30s is when most experience or notice some of the signs of aging. From increased difficulty controlling blood pressure, to skin sagging, to joint pain, all the way down to our nervous system, our bodies give off several signs that you are getting older. What causes this to happen? With age, bones density diminishes, which causes weakening and makes you more susceptible to a fracture. Muscle mass begins to atrophy, and these are factors that affect our overall coordination, stability and balance. Because of this, scientists are in a race to try to maintain and hopefully elongate the average healthspan, or years we are in good health, for both men and women. Simply living longer is not an option many people are excited about. Most people only desire to live as long as they can, but while still in good health that allows them to enjoy their favorite activities. Finding a solution to slow down the negative effects of aging is a focus for many leading longevity scientists who are searching for new technologies and investing in cellular health research. But what if the answer was simple and rooted in an everyday nutrient that is simple to supplement our diets with?


Aging: The Root Cause of Disease

Genetics, evolution and environment play a major role in aging. However, age is the predominant risk factor for prevalent diseases. Aging results from the accumulation of molecular and cellular damage overtime. The cells in the human body already have a predetermined lifespan. A process called apoptosis is used to get rid of the cells that are no longer needed or have been damaged beyond repair. As we age, this process becomes difficult because our bodies no longer function the same. These stressed cells become enlarged and irregular and are no longer able to divide. One of the hallmarks of aging is cellular senescence, where arrest of the cell cycle is triggered and damaged cells prevented from further grow and divide. As the aging immune system becomes less effective, senescent cells accumulate and can harm the healthy cells. This may lead to affecting a person’s ability to withstand illness or recuperate from injuries. Senescent cells are unique from normal cells because even after they stop multiplying and do not die off. These senescent cells stay in the body and continue to release soluble factors that can circulate throughout the body and trigger inflammation, which can further spread senescence or induce cell death. In 2021, I published a study on how senescent cells exacerbate COVID-19. The number of senescent cells in our body increases with age, making us more prone to “inflammaging” and leading to age-related diseases. Preclinical studies support the notion that an increase in senescent cells may be a reasonable root cause of chronic disease as we age.


Senolytics: A Promising Candidate

Senescent cells have earned the nickname “zombie cells,” because like zombies, senescent cells are old dysfunctional cells that “never die”. “Zombie cells” can accumulate throughout the body and can cause damage to healthy cells. Drugs called senolytics are being identified as a solution in this quest for healthy aging and are designed to selectively eliminate the “zombie cells.” When a team of researchers and I conducted a trial on old mice infected with a coronavirus, treatment with senolytics reduced mortality and increased antiviral antibodies, which increased their survival rate to 50%. What the study suggests is that, in humans, the reason older people may have a more difficult time with recovering from viruses, like SARS-CoV2, is because of the senescent cell burden associated with older age. Reducing that burden of senescent cells could reduce the risk of dying from COVID-19 or mitigate some effects of long COVID.

Some examples of senolytics are dasatinib and quercetin or fisetin. Additionally, senescent cells have been linked to typical age-related chronic conditions, like frailty, cognitive impairment, inflammation and chronic diseases. Early senolytics trials suggest that senolytics decrease senescent cell burden, reduce inflammation and alleviate frailty in humans. One senolytic that has been getting more attention is a natural nutrient, fisetin. This is a plant-based polyphenol flavonoid that can be found in many fruits and vegetables such as strawberries, apples, persimmons, onions and cucumbers. It is a natural senolytic that may reduce the number of senescent cells that accumulate as we age and support normal antioxidant synthesis, which is the body’s natural defense against harmful chemicals and is used to protect our body from macromolecular damage and sustain cellular homeostasis. Although fisetin can be found in fruits and vegetables, it is nearly impossible to get enough of this nutrient through food alone.


Supplementation: What Works Against Aging?

Currently, the Mayo clinic is conducting a trial on how fisetin helps with frailty in older adults and a separate trial to investigate the use of fisetin in older women to remove senescent cells to confirm if it has health benefits. What we are learning is that daily supplementation with fisetin could play a critical role in the fight against zombie cells. I have been advising SRW Laboratories on the development of their fisetin supplement, Cel3 Renewal, which is designed to reduce senescent cell burden in the body. Cel3 Renewal also supports autophagy, the intracellular recycling program that functions in our cells to remove damaged or dysfunctional proteins. The three main ingredients in Cel3 Renewal that help to optimize cellular function include apigenin, fisetin and oleuropein. Having led numerous projects and extensive research on the effectiveness of fisetin and how it may support both the healthspan and lifespan for men and women. The possible beneficial effects of fisetin that can support healthy aging, resulting in a longer healthspan.


Aging: The Future

The field of geroscience, the study of aging, is growing every day. With all this science and research occurring in the field of aging, we are learning more about how we age and how we can intervene to delay the onset or alleviate the pathology of aging. The goal of geroscience is to attenuate some of the most deleterious effects of aging so that we can reach a state of being “wellderly.” Fisetin supplementation and a healthy lifestyle may have the potential to bring several positive health benefits for your body as you age. There are many tools and supplements now at our disposal that we know work, from fasting, to exercising, getting plenty of sleep, stress reduction techniques and exciting nutraceuticals that can selectively get rid of “zombie cells,” like fisetin. We should take advantage of all the science and education that has emerged on aging and put it to work for us so that we can make living well the focus of the last decades of our life.

Dr. Matthew Yousefzadeh has published more than 30 scientific publications with heavy emphasis on cellular senescence and aging. Dr. Yousefzadeh has led numerous projects researching the efficacy of Fisetin and how it supports healthspan and lifespan. He serves on the scientific advisory board for SRW Laboratories. You can connect with Dr. Matthew Yousefzadeh at: https://scienceresearchwellness.com/pages/matt-yousefzadeh

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