This article explores the anti-aging potential of fisetin, a natural compound, focusing on its role in senescence, a key hallmark of aging. It begins by noting that the accumulation of senescent cells, also known as “zombie cells,” secretes harmful substances that trigger chronic inflammation, damaging surrounding healthy cells and stem cells, thus driving aging and related diseases.
From the ancient alchemists' quest for the elixir of life to modern-day scientists in state-of-the-art labs, humanity’s pursuit of "immortality" has never ceased. Today, anti-aging is no longer just about luxury skincare products or wellness secrets—it has evolved into a booming industry.
According to authoritative institutions, the global anti-aging market is expected to surpass hundreds of billions of dollars in the near future, spanning drug development, health technologies, and nutritional supplements.
One of the key targets in aging research is the so-called “zombie cells”—senescent cells, and one such natural compound—fisetin, found in everyday fruits like strawberries and apples—is emerging as a powerful player in clearing these senescent cells. Fisetin offers a new approach in the anti-aging research arena, bringing the “youthful secrets in your fruit bowl” closer to reality.
1. Cellular Senescence and Aging
Cellular senescence has become a focal point in anti-aging research. Normally, when cells become old or dysfunctional, they die, making space for new cells to thrive.
However, as we age, many cells instead enter a state of senescence, meaning they lose their ability to divide or perform essential functions but resist cell death, leading to overcrowding. Some scientists have dubbed these senescent cells “zombie cells.” These cells not only linger in the body but also secrete toxic compounds that degrade surrounding healthy cells and induce chronic inflammation, causing systemic damage.
2. Fisetin: A Natural Anti-Aging Compound
Recent studies have revealed that fisetin, a powerful anti-aging substance, excels in clearing senescent cells. Compared to other plant compounds, such as quercetin, fisetin has shown remarkable effectiveness in eliminating senescent cells in both cell cultures and animal models.
Fisetin is a plant polyphenol and flavonoid compound found in many trees and plants, including several eudicotyledons, acacias, sumac, and pistachio trees. The first recorded isolation of fisetin dates back to 1833, and its basic chemical properties were defined by J. Schmidt in 1886, with S. Kostanecki further elucidating its chemical structure and synthesis in the 1890s. Fisetin is now recognized as a secondary metabolite in many plants, including its presence in green parts, fruits, bark, and hardwoods of various species. It is also abundant in fruits and vegetables like strawberries, apples, persimmons, grapes, onions, and cucumbers.
3. How Fisetin Combats Aging
Through animal studies and some clinical trials, scientists have identified several mechanisms by which fisetin may contribute to lifespan extension. Here are the five key anti-aging effects of fisetin:
1) Eliminating Senescent Cells
As mentioned earlier, senescent cells secrete harmful substances that damage surrounding healthy cells and stem cells, making the body more susceptible to diseases, especially cancer. Fisetin’s ability to eliminate senescent cells has been shown to significantly improve the lifespan of mice. In one study, mice given fisetin lived an average of 2.5 months longer, representing a nearly 10% extension of their lifespan.
2) Improving Cognitive Decline
Another intriguing aspect of fisetin is its potential to reduce cognitive aging in mice. One study found that aged mice, after receiving fisetin, demonstrated improved abilities to navigate mazes and recognize objects. This suggests that fisetin may enhance cognitive functions and memory. Furthermore, the cognitive and memory abilities of aged mice became nearly indistinguishable from those of younger mice.
According to research, fisetin may extend both the median and maximum lifespan of mice, even when administered in their later years (equivalent to humans in their 50s or 60s). Additionally, fisetin has shown potential in preventing cognitive and memory disorders in models of early-onset Alzheimer’s disease.
3) Preventing Wrinkles Caused by UVB Exposure
Fisetin also plays a role in reducing the formation of wrinkles and enhancing skin health. This is achieved by reducing the number of matrix metalloproteinases (MMPs), enzymes that break down the extracellular matrix around cells. The extracellular matrix includes collagen, elastin, hyaluronic acid, and other molecules that bind with cells to keep tissues like skin and organs firm. Excessive MMP activity can lead to the formation of wrinkles, but fisetin helps reduce this process.
4) Inhibiting Cancer Cells
Reports indicate that fisetin can prevent cancer and limit the growth and spread of existing tumors. It induces apoptosis (programmed cell death) in cancer cells, which helps eliminate malignant cells. Additionally, as an anti-inflammatory agent, fisetin can reduce compounds that exacerbate chronic inflammation and promote cancer progression.
5) Supporting Bone Health Against Osteoporosis
Osteoporosis, a condition characterized by fragile bones, is another sign of aging, and fisetin proves beneficial in combating this condition. Osteoblasts, the cells responsible for bone formation, and osteoclasts, which break down bone tissue, work in tandem to maintain bone health. In osteoporosis, osteoclasts become more active than osteoblasts. Studies in rats have shown that fisetin can stimulate osteoblast activity while inhibiting osteoclast activity, helping to prevent osteoporosis.
Conclusion
Fisetin’s promising effects in improving health and reversing aging mechanisms have made it a subject of increasing interest in the scientific community. To date, fisetin has shown great potential in extending lifespan and healthspan by targeting senescent cells and mitigating age-related conditions. As research continues to explore its full capabilities, fisetin could become a key player in the fight against aging.
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Krishnakumar, I. M., Jaja-Chimedza, A., Joseph, A., et al. (2022). Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomized double-blinded comparative crossover study. Journal of Nutritional Science, 74(11).
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Park, J. H., Jang, Y. J., Choi, Y. J., et al. (2013). Fisetin inhibits matrix metalloproteinases and reduces tumor cell invasiveness and endothelial cell tube formation. Nutr Cancer, 65(8), 1192–1199.
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Syed, D. N., Adhami, V. M., Khan, M. I., et al. (2013). Inhibition of Akt/mTOR signaling by the dietary flavonoid fisetin. Anticancer Agents Med Chem., 13(7), 995–1001.