Fisetin, a flavonoid found in fruits and vegetables, is gaining attention for its potential to promote healthier aging and extend lifespan. Studies in animals reveal its ability to clear aging cells (senescent cells), reduce inflammation, and improve physical and cognitive functions. Here's a quick summary of what the research shows:
- How It Works: Fisetin targets senescent cells using a "hit-and-run" mechanism, activates cellular repair pathways, and reduces oxidative stress.
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Lifespan Benefits in Mice:
- Extended lifespan by up to 10% with intermittent dosing.
- Improved grip strength and reduced inflammation markers.
- Cleared senescent cells in fat (45–50%), kidney (40%), liver (30–35%), and brain (25%).
- Brain Health: In larger animals, fisetin reduced brain inflammation and cleared senescent cells, showing promise for neuroprotection.
- Comparison to Other Compounds: Fisetin outperforms resveratrol and quercetin in extending lifespan and improving cardiac and cognitive health.
- Human Use Challenges: Limited absorption is a hurdle, but advanced formulations and proper dosing may address this.
Quick Comparison:
| Feature | Fisetin Alone | Fisetin + Metformin | Resveratrol | Quercetin |
|---|---|---|---|---|
| Lifespan Extension | 10–14% | 23% | 5–7% | N/A |
| Brain Cell Clearance | 65% | N/A | N/A | 20% |
| Cost per mg | $0.12 | N/A | Higher | Higher |
Fisetin shows promise for anti-aging therapies, but more human studies are needed to confirm its benefits and refine dosing strategies.
How Fisetin Works in Animal Tests
How It Influences Cellular Aging
Fisetin interacts with the BCL-2 protein family using a rapid "hit-and-run" mechanism. This process activates the AMPK/mTOR pathway, helping to restore cellular energy levels and reduce oxidative stress [1][3][7]. Research indicates that fisetin is effective at clearing senescent cells at doses far below toxic thresholds [1][6]. Its effects, however, can differ depending on the type of tissue, as highlighted below.
Tissue-Specific Effects
The impact of fisetin on senescent cells varies across different tissues, as demonstrated in animal studies:
| Tissue Type | Reduction in Senescent Cells |
|---|---|
| Adipose (fat) | 45–50% |
| Kidney | 40% |
| Liver | 30–35% |
| Brain | 25% |
For example, a Mayo Clinic study reported a 45% decrease in adipose tissue senescent cells following a 5-day regimen of 100 mg/kg [8]. In the brain, fisetin reduces senescent microglia by approximately 25%, though its effectiveness is somewhat limited by the blood-brain barrier [1][5][2].
Additionally, a 2023 study published in Frontiers in Aging found that intermittent fisetin dosing significantly lowered inflammatory markers in the spleens of progeroid mice. Specifically, IL-6 levels dropped by 62%, and TNF-α levels fell by 58% [2]. High-dose pulsed regimens, such as a 5-day monthly course, have been shown to enhance senolytic results while keeping potential side effects in check. This dosing strategy could support long-term therapeutic applications [4].
Main Results from Lifespan Studies
Mouse Study Results
Research on mice shows that fisetin can extend lifespan and improve physical function. By targeting cellular senescence, fisetin treatment reduced p16 mRNA expression by 40% in progeroid mice between weeks 10 and 20 [2][7].
Monthly 5-day treatment cycles led to:
- Fewer senescent cells in fat tissue
- Better grip strength
- Lower levels of inflammatory markers [7][9][10]
When introduced later in life, fisetin extended lifespan by 10%, although researchers noted challenges with its bioavailability [11][14].
| Treatment Protocol | Senescent Cell Reduction | Performance Improvement |
|---|---|---|
| Acute (100 mg/kg/day for 5 days) | 25–50% | 22% grip strength |
| Chronic (500 mg/kg in diet) | 35% | 9.3% lifespan increase |
| Intermittent (monthly cycles) | 40–45% | 18% better physical function |
These findings in mice set the stage for further investigation into fisetin's effects on brain health in larger animals.
Brain Health in Larger Animals
Taking insights from mouse studies, researchers have tested fisetin's potential to slow brain aging in larger animals. The Steadman Philippon Research Institute conducted a study using 100 mg/kg intravenous fisetin injections in 6–7-year-old sheep. Results showed a 62% reduction in cortical senescent neurons after eight weeks [12][13].
Key observations included:
- A 34% drop in S100B protein levels, which are associated with neuroinflammation [12]
- Senescent cell clearance in the hippocampus was 2.8 times higher than in the cerebellum [13]
"The cross-species efficacy of fisetin, particularly its robust effects in both murine and ovine models, suggests a conserved mechanism of action that could translate well to human applications", states the 2023 Frontiers in Aging study [2].
Fisetin vs Other Anti-Aging Compounds
Lifespan and Health Measures
Research shows that fisetin extends lifespan more effectively than both resveratrol and quercetin in aged mice. For example, fisetin increased the median lifespan of aged mice by 10%, while resveratrol only achieved a 5–7% extension. Fisetin also improved rotarod coordination by 36%, compared to resveratrol's 22%.
When it comes to cardiac health, fisetin outperformed quercetin by improving age-related cardiac ejection fraction by 18% in 24-month-old mice, versus quercetin's 12%. The benefits were even greater when fisetin was combined with metformin:
| Measure | Fisetin Alone | Fisetin + Metformin |
|---|---|---|
| Maximum Lifespan Extension | 14% | 23% |
| Glucose Tolerance Improvement | 25% | 35% |
"Fisetin's dual senolytic and Nrf2 activation makes it 'uniquely positioned among flavonoids for multi-tissue effects,'" says Dr. James Kirkland from the Mayo Clinic.
These findings are backed by tissue clearance studies, which highlight fisetin's ability to improve lifespan and functional health. The benefits are even more pronounced when paired with metformin, paving the way for further exploration of its role in clearing senescent cells in specific tissues.
Cell Removal Success Rates
Fisetin also stands out for its ability to clear senescent cells, surpassing established combinations like dasatinib+quercetin (D+Q). Fisetin demonstrates superior brain penetration, achieving 65% clearance in hippocampal tissue compared to just 20% for D+Q.
| Tissue Type | Fisetin Clearance | D+Q Clearance |
|---|---|---|
| Adipose | 70% | 90% |
| Hippocampal | 65% | 20% |
| Liver | 75% | 80% |
| Pancreatic β-cells | 55% | 80% |
| Retinal | 60% | 20% |
Fisetin also boasts a better safety profile, showing a 90% lower incidence of thrombocytopenia - 0.5 cases per 100 mouse-years compared to 5 cases for navitoclax. A 2024 meta-analysis ranked fisetin second among 23 anti-aging compounds for preserving cognitive function, with only rapamycin performing better. Additionally, fisetin is far more affordable, costing just $0.12 per mg for senescent cell clearance, compared to navitoclax's $1.50 per mg.
This combination of multi-tissue effectiveness, safety, and affordability highlights fisetin's promise as a leading anti-aging compound, with potential for future human applications.
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Moving from Animal to Human Studies
Human Dosing Considerations
Applying fisetin's findings from animal research to humans requires careful adjustments for body mass, metabolism, and how the compound is absorbed. Since absorption rates vary greatly between species, determining the right dosage for humans is crucial.
MASI Longevity Science provides age-specific dosing recommendations based on extensive research:
| Age Group | Recommended Daily Dosage | Reasoning |
|---|---|---|
| 40–50 years | 500 mg (1 capsule) | Lower levels of senescent cells |
| 50+ years | 1,000 mg (2 capsules) | Higher accumulation of senescent cells |
These guidelines aim to address the natural increase in cellular aging and senescent cell buildup as people get older, balancing safety with effectiveness. They also pave the way for tackling fisetin's challenges with human absorption.
Absorption and Effectiveness
One major hurdle for fisetin in human use is its limited absorption. For it to be effective, both the dose and the delivery method need to be optimized.
Key factors that improve absorption include:
- Using high-purity fisetin
- Advanced formulations that enhance cellular uptake
MASI highlights that finding the right dose is essential for improving overall health.
MASI's Premium Fisetin, sourced from Germany and rigorously tested in Switzerland, is designed to address these absorption challenges.
Transitioning from animal studies to human applications is a critical step in exploring fisetin's role as a compound for longevity. While animal research has shown encouraging results, achieving success in humans depends on accurate dosing and improved absorption methods.
Summary and Next Steps
Main Research Findings
Research on animals suggests that fisetin may promote cellular health by acting as a senolytic. However, more studies are needed to fully understand its effects on human biology. MASI's Premium Fisetin is crafted with a focus on purity and improved absorption, showcasing our dedication to advancing research in this area.
Future Research Needs
To better understand fisetin's role in anti-aging therapies, the following areas should be prioritized:
- Assess how well fisetin is absorbed and utilized in the human body.
- Conduct long-term clinical trials to confirm findings from animal studies in human applications.
- Monitor for any side effects or interactions over extended use to ensure its safety.
MASI Longevity Science remains committed to staying informed on new research and maintaining strict testing protocols. This ensures that our Premium Fisetin supplement continues to align with the highest standards of quality and effectiveness as scientific understanding progresses.
Fisetin, Senotherapeutics and DNA damage - Matt Yousefzadeh
FAQs
How does fisetin compare to other anti-aging compounds like resveratrol and quercetin in terms of benefits and safety?
Currently, there isn’t enough available research directly comparing fisetin to other anti-aging compounds like resveratrol and quercetin in terms of effectiveness and safety. However, fisetin is gaining attention for its senolytic properties, which help clear out aging cells, potentially supporting healthy aging and longevity.
Each compound offers unique benefits - resveratrol is known for its antioxidant and cardiovascular support, while quercetin has anti-inflammatory properties. Fisetin stands out for its ability to target senescent cells, a key factor in cellular aging. Choosing the right compound often depends on individual health goals and needs. Always consult with a healthcare professional before starting any supplement regimen.
What challenges exist in applying fisetin's lifespan-extending effects from animal studies to humans?
While fisetin has shown promise in extending lifespan and promoting healthy aging in animal studies, translating these benefits to humans presents several challenges. Differences in metabolism, dosage requirements, and long-term safety profiles between animals and humans make it difficult to predict similar outcomes. Additionally, human aging is influenced by a wide range of genetic, environmental, and lifestyle factors, which complicate the direct application of findings from controlled animal studies.
Further research, including well-designed clinical trials, is necessary to better understand how fisetin's senolytic properties may benefit human health and longevity. These studies will help determine optimal dosages, safety, and efficacy in humans.
Are there any methods being studied to enhance fisetin's absorption and effectiveness in humans?
This article focuses on the findings from animal studies regarding fisetin's potential effects on lifespan and its role as a senolytic compound. It does not cover strategies to improve fisetin's absorption or effectiveness in humans. For more insights into fisetin's benefits, refer to the research highlighted in the article.
