Fisetin, Quercitin: Elixir of Longevity

By Gabcom

The idea of an "elixir of longevity" has been a part of myths, legends, and various cultural traditions for centuries. In ancient times, many civilizations, including the Chinese, Egyptians, and Greeks, believed in the existence of a substance that could grant immortality or significantly extend life. Alchemists, particularly in medieval Europe and China, sought the philosopher's stone or the elixir of life, believed to bestow eternal youth and health.
Modern Science on Longevity:

Today, while there's no magical elixir that can grant immortality, significant research is being conducted on extending human lifespan and improving the quality of life in old age. Here are some key areas of research:

Telomeres and Aging: Telomeres are protective caps on the ends of chromosomes that shorten as cells divide. When they become too short, cells can no longer divide, leading to aging. Scientists are exploring ways to maintain or lengthen telomeres, which could potentially slow down the aging process.


Caloric Restriction: Studies in animals have shown that reducing calorie intake without malnutrition can extend lifespan. Research is ongoing to see if similar effects can be achieved in humans.


Senolytics: These are drugs that target and eliminate senescent cells, which are cells that have stopped dividing and contribute to aging and age-related diseases. Removing these cells has shown promise in extending lifespan in animal studies.


Genetic and Epigenetic Interventions: Scientists are exploring the role of genes and epigenetic changes (changes in gene expression without altering the DNA sequence) in aging. Interventions that target specific genes or modify epigenetic markers could potentially extend lifespan.


Regenerative Medicine: Advances in stem cell therapy and tissue engineering hold the promise of regenerating damaged tissues and organs, potentially extending healthy lifespan.


Antioxidants and Supplements: Some believe that certain antioxidants and supplements can slow the aging process by reducing oxidative stress in the body. However, the effectiveness of many of these supplements remains unproven.
Current Limitations:

While science is making strides, there are still significant challenges. The aging process is complex, involving many factors, including genetics, lifestyle, and environmental influences. Extending lifespan without compromising the quality of life is a significant concern.

In conclusion, while an actual "elixir of longevity" as imagined in legends is unlikely, ongoing research is exploring ways to extend healthy lifespan and improve the aging process.




Senolytics

Senolytics are a class of drugs that target and eliminate senescent cells, which are cells that have stopped dividing but haven't died off. These senescent cells accumulate in the body as we age, contributing to various age-related diseases and overall aging by secreting harmful substances that can damage surrounding tissues and promote chronic inflammation.



How Senolytics Work

Senolytics work by selectively inducing apoptosis (programmed cell death) in senescent cells without affecting normal, healthy cells. By clearing out these aged cells, senolytics aim to reduce the burden of senescence on the body, potentially delaying the onset of age-related diseases and extending the healthy lifespan.
Key Research and Developments

Early Studies: The concept of senolytics emerged around 2015 when researchers discovered that certain compounds could selectively target senescent cells in mice. The initial studies showed that removing these cells could improve various aspects of health, such as cardiovascular function, kidney function, and physical endurance.


Potential Compounds:

Dasatinib: Originally a cancer drug, dasatinib has been shown to clear senescent cells, particularly in the cardiovascular system.


Quercetin: A natural flavonoid found in many fruits and vegetables, quercetin has been found to have senolytic properties, particularly in combination with dasatinib.


Fisetin: Another natural compound with senolytic properties, fisetin is found in strawberries, apples, and other fruits. It has shown promise in reducing the number of senescent cells in animal models.


Human Trials: While most research has been conducted in animals, early-stage clinical trials in humans are underway to test the safety and efficacy of senolytic therapies. These trials are still in the preliminary stages, but the results so far are promising.


Applications: Beyond anti-aging, senolytics have potential applications in treating a range of age-related diseases, including:

Osteoarthritis: By clearing senescent cells in joints, senolytics could potentially reduce inflammation and pain associated with osteoarthritis.


Fibrosis: Senolytics might help reduce fibrosis (scarring) in organs like the liver, lungs, and kidneys, which is a common problem in aging.


Neurodegenerative Diseases: There is interest in exploring senolytics for treating neurodegenerative diseases like Alzheimer's, where senescent cells contribute to brain inflammation and degeneration.



Challenges and Considerations

Targeting: One of the challenges is ensuring that senolytics effectively target senescent cells without affecting healthy cells, as the wrong targeting could lead to unintended side effects.


Timing and Dosage: Determining the optimal timing and dosage for administering senolytics is another challenge. Overuse could lead to potential toxicity or other adverse effects.


Long-Term Effects: Since senolytics are a relatively new area of research, the long-term effects of these treatments are not yet fully understood.
Conclusion

Senolytics represent a promising new avenue in the quest to extend healthy lifespan and treat age-related diseases. While still in the experimental stage, these therapies have the potential to significantly impact the way we approach aging and age-related health issues. However, more research is needed to fully understand their safety, efficacy, and long-term effects.




Senolytic Drugs

As of now, senolytic drugs are mostly in the experimental or early clinical trial stages. However, a few compounds have shown senolytic properties and are being investigated for their potential to target senescent cells. Some of these drugs are repurposed from other treatments, while others are natural compounds. Here are the most notable ones:
1. Dasatinib (Sprycel)

Original Use: Dasatinib is an FDA-approved drug primarily used to treat certain types of leukemia (chronic myeloid leukemia and acute lymphoblastic leukemia).


Senolytic Activity: In research, dasatinib has been shown to selectively target and eliminate senescent cells, particularly those in the cardiovascular system and fat tissue.


Availability: Dasatinib is available by prescription for cancer treatment, but its use as a senolytic is still under investigation and is not yet approved for this purpose.



2. Quercetin

Original Use: Quercetin is a natural flavonoid found in many fruits and vegetables, like apples, onions, and berries. It is commonly available as a dietary supplement for its antioxidant properties.


Senolytic Activity: Quercetin has been shown to have senolytic effects, particularly when combined with dasatinib. It can target senescent endothelial cells and has been studied in the context of cardiovascular aging.


Availability: Quercetin is widely available as an over-the-counter dietary supplement.
3. Fisetin

Original Use: Fisetin is another natural flavonoid found in fruits such as strawberries, apples, persimmons, and cucumbers. It is also available as a dietary supplement.


Senolytic Activity: Fisetin has shown potential in clearing senescent cells and has demonstrated positive effects on lifespan and healthspan in animal studies.


Availability: Fisetin is available as an over-the-counter supplement, though its use as a senolytic is still being studied.
4. Navitoclax (ABT-263)

Original Use: Navitoclax is a drug initially developed for cancer treatment, specifically to target B-cell lymphoma.


Senolytic Activity: Navitoclax has shown promise in clearing senescent cells, particularly those related to hematopoietic (blood-forming) tissues and other organs. However, it is known to have significant side effects, such as reducing platelet counts, which limits its use.


Availability: Navitoclax is not widely available outside of clinical trials due to its toxicity and side effects.
5. Piperlongumine

Original Use: Piperlongumine is a natural compound derived from the long pepper plant (Piper longum). It has been studied for its anti-cancer and anti-inflammatory properties.


Senolytic Activity: It has shown some ability to target and eliminate senescent cells in laboratory studies, though more research is needed to confirm its efficacy and safety as a senolytic agent.


Availability: Piperlongumine is not commonly available as a supplement or drug and is primarily used in research contexts.
6. FOXO4-DRI Peptide

Original Use: This is a synthetic peptide designed specifically to interfere with the interaction between the FOXO4 protein and p53, a protein involved in cell cycle regulation and apoptosis.


Senolytic Activity: FOXO4-DRI has been shown in preclinical studies to induce apoptosis in senescent cells without harming healthy cells. It is particularly targeted at neurodegenerative and other age-related conditions.


Availability: FOXO4-DRI is still in the experimental stage and is not available for general use.
Important Considerations

Clinical Use: While some of these compounds are available as dietary supplements (like quercetin and fisetin), others are only available through clinical trials or off-label use with a prescription (like dasatinib). The use of these compounds as senolytics is still in the early stages, and they are not yet approved for anti-aging purposes.


Side Effects: Some senolytics, particularly those originally designed as cancer drugs, can have significant side effects. It is important to approach the use of any senolytic compounds with caution and under medical supervision if they are being used outside of clinical trials.


Research Status: The field of senolytics is rapidly evolving, and ongoing research may lead to new discoveries or better compounds with fewer side effects.

Several natural compounds have been identified as having potential senolytic properties, meaning they can selectively target and eliminate senescent cells. These compounds are generally found in foods and plants, and some are available as dietary supplements. Here are the most notable natural senolytics:



1. Fisetin

Source: Fisetin is a flavonoid found in strawberries, apples, grapes, persimmons, onions, and cucumbers.


Senolytic Activity: Fisetin has shown strong senolytic effects in preclinical studies, including extending lifespan and improving healthspan in animal models. It can reduce the number of senescent cells in various tissues and has anti-inflammatory and antioxidant properties.


Availability: Fisetin is available as a dietary supplement.
2. Quercetin

Source: Quercetin is another flavonoid found in many fruits and vegetables, including apples, onions, berries, and leafy greens.


Senolytic Activity: Quercetin has been studied for its ability to clear senescent cells, especially when combined with dasatinib. It has also been shown to improve cardiovascular health, reduce inflammation, and provide antioxidant benefits.


Availability: Quercetin is widely available as an over-the-counter supplement.
3. Piperlongumine

Source: Piperlongumine is a natural compound derived from the long pepper plant (Piper longum), commonly used in traditional medicine.


Senolytic Activity: Piperlongumine has shown some ability to target senescent cells by inducing oxidative stress specifically in these cells, leading to their apoptosis (programmed cell death). It also has potential anti-cancer and anti-inflammatory properties.


Availability: Piperlongumine is less commonly available as a supplement and is mainly studied in research contexts.
4. Curcumin

Source: Curcumin is the active compound in turmeric, a spice commonly used in Indian and Southeast Asian cooking.


Senolytic Activity: Curcumin has demonstrated potential in reducing the accumulation of senescent cells, particularly in skin and adipose tissues. It is also known for its anti-inflammatory, antioxidant, and anti-cancer properties.


Availability: Curcumin is widely available as a dietary supplement, often in the form of turmeric extracts.
5. Apigenin

Source: Apigenin is a flavonoid found in parsley, chamomile, celery, and other plant-based foods.


Senolytic Activity: Apigenin has been studied for its ability to promote cell cycle arrest and apoptosis in cancer cells and may have senolytic effects by reducing oxidative stress and inflammation in senescent cells.


Availability: Apigenin is available as a dietary supplement.
6. Resveratrol

Source: Resveratrol is a polyphenol found in red grapes, red wine, berries, and peanuts.


Senolytic Activity: Resveratrol has been widely studied for its anti-aging effects, including its ability to activate certain genes involved in longevity (such as SIRT1) and reduce senescence markers. It also has antioxidant and anti-inflammatory properties.


Availability: Resveratrol is available as a supplement.
7. EGCG (Epigallocatechin gallate)

Source: EGCG is a catechin found in high concentrations in green tea.


Senolytic Activity: EGCG has been shown to have potential senolytic effects by reducing oxidative stress and inflammation, which are key contributors to cellular senescence. It may help eliminate senescent cells, particularly in skin and cardiovascular tissues.


Availability: EGCG is available as a supplement, often in the form of green tea extracts.
8. Gingerol

Source: Gingerol is the active compound in ginger.


Senolytic Activity: Gingerol has been noted for its anti-inflammatory and antioxidant properties, which can indirectly help reduce the burden of senescent cells. Some studies suggest it may have a role in promoting healthy aging and reducing chronic inflammation.


Availability: Gingerol is present in fresh ginger or available in concentrated supplement form.
Considerations

Research Stage: While these natural compounds show promise as senolytics, most of the research is still in the early stages, particularly in humans. Many of these studies have been conducted in cell cultures or animal models, so the full effects in humans are not yet completely understood.


Safety and Dosage: Natural compounds can have potent biological effects, so it’s essential to consider the appropriate dosage and potential interactions with other medications. Consulting with a healthcare provider before starting any new supplement is advised.




Natural senolytics like fisetin, quercetin, and curcumin offer a potentially accessible way to help manage aging and related diseases by reducing the burden of senescent cells. While promising, further research and clinical trials are needed to confirm their efficacy and safety in humans.




Fisetin

Fisetin is a natural flavonoid found in various fruits and vegetables and has gained attention for its potential senolytic properties, which means it may help clear senescent cells that contribute to aging and age-related diseases. While fisetin is available as a dietary supplement, its use as a senolytic is still under research, and there are no officially established guidelines for its dosage and administration. However, based on current studies and available information, here are some considerations for using fisetin:
1. Dosage

Standard Supplement Dosage: Fisetin supplements are typically available in doses ranging from 100 mg to 500 mg per capsule or tablet. For general antioxidant or anti-inflammatory purposes, a lower dose (100-250 mg per day) is often recommended.


Senolytic Dosage: Some research studies and experimental protocols for senolytic purposes have used higher doses, typically around 20 mg per kilogram of body weight per day. This can translate to a total daily dose of 1,000-2,000 mg for an average adult, taken for a few consecutive days.


Cycle Approach: In the context of senolytic use, fisetin is often taken in a "hit-and-run" approach, where a high dose is consumed for a few days (e.g., two to three days) and then discontinued. This cycle might be repeated every few months, depending on individual health goals and emerging research.
2. Timing

Fisetin can be taken with or without food, although some recommend taking it with a meal that contains healthy fats, as flavonoids like fisetin may have better absorption when consumed with fat.


Time of Day: There’s no specific time of day that has been proven to be better for fisetin supplementation. It can be taken in the morning or evening, based on personal preference and convenience.
3. Combination with Other Supplements

Quercetin: Fisetin is sometimes used in combination with quercetin, another flavonoid with senolytic properties, to potentially enhance the senolytic effect.


Dasatinib: In experimental research, fisetin is not commonly combined with dasatinib (a cancer drug with senolytic effects), but quercetin often is. It’s important to approach combinations carefully, particularly with more potent pharmaceutical drugs.
4. Safety and Side Effects

Side Effects: Fisetin is generally considered safe, with few reported side effects. Some users might experience mild digestive discomfort or headaches at higher doses.


Consultation with Healthcare Provider: It’s crucial to consult with a healthcare provider before starting fisetin, especially at higher doses, to ensure it’s safe based on your health status and other medications or supplements you might be taking.


Monitoring: If you are using fisetin for its senolytic effects, consider regular check-ins with your healthcare provider to monitor any potential effects on your health, particularly if taking high doses periodically.
5. Purchasing and Quality

Supplement Quality: Look for high-quality fisetin supplements from reputable brands that provide third-party testing to ensure purity and potency.


Formulation: Fisetin is available in various forms, including capsules, tablets, and powders. Choose the form that best fits your lifestyle and ease of use.
6. Research and Emerging Guidelines

The field of senolytics is rapidly evolving, and more research is needed to establish standardized guidelines for the use of fisetin and other senolytic compounds in humans. Keep an eye on emerging studies and recommendations to stay informed about best practices.

Using fisetin, particularly for its potential senolytic effects, is an area of active research. While it shows promise, the optimal dosage, timing, and frequency are not yet fully established. If considering fisetin for senolytic purposes, consult with a healthcare professional, start with a moderate dose, and monitor your response carefully.
Fruits with Higher Fisetin Content

For those specifically looking to increase their fisetin intake through natural sources, the following fruits are known to have higher concentrations of fisetin:

Strawberries: One of the richest natural sources of fisetin.


Apples: Particularly the skin of apples contains a good amount of fisetin.


Persimmons: Another fruit that contains fisetin, although in smaller amounts than strawberries.


Grapes: Red grapes, in particular, contain some fisetin, although it's more commonly associated with resveratrol.







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About the Researcher




GabrieL Comia Jr is a student in Alchemistry.