Fisetin for Anti-Aging: Brain, Heart, Skin and Metabolic Benefits from Published Research

TL;DR: Fisetin is a strawberry-derived flavonoid with a unusually broad set of anti-aging mechanisms in the lab: it clears senescent cells, activates the Nrf2 antioxidant pathway, dampens neuroinflammation and protects skin from UV damage. Human trials are now testing whether these effects translate into better vascular function, mobility, cognition and biological-age markers. As of 2026, fisetin is promising but unproven as a human longevity intervention.

1. What Is Fisetin?

Fisetin is a dietary flavonoid — a yellow plant pigment — found in strawberries, apples, grapes, persimmons, cucumbers, tomatoes and onions. It belongs to the flavonol subclass, alongside quercetin and kaempferol.

Like many polyphenols, fisetin has antioxidant and anti-inflammatory activity. What has set it apart in geroscience is a series of papers suggesting it can selectively kill senescent cells while leaving healthy cells largely untouched, earning it the label senolytic. Read our deeper dive on fisetin as a senolytic for the full trial and dosing picture.

This article focuses on fisetin's broader anti-aging profile: brain, cardiovascular, skin and metabolic health, plus the human trials that are currently asking whether those benefits are real.

2. Mechanisms: How Fisetin Might Target Ageing

Several pathways have been identified in published preclinical work:

• Senolysis: fisetin can induce apoptosis in senescent cells by modulating pro-survival pathways such as BCL-2 and lowering senescence-associated secretory phenotype (SASP) signalling (Yousefzadeh et al., 2018).
• Nrf2 activation: fisetin upregulates the Nrf2 antioxidant response element, increasing glutathione-related defences and reducing oxidative stress in neurons, endothelial cells and skin.
• Anti-inflammatory signalling: it inhibits NF-κB and downstream cytokines such as IL-6, TNF-α and IL-1β, which are elevated in "inflammageing."
• Sirtuin/AMPK crosstalk: some studies report fisetin can increase SIRT1 activity and AMPK phosphorylation, pathways linked to metabolic health and mitochondrial function.
• Direct antioxidant scavenging: fisetin neutralises reactive oxygen species (ROS), although this is less clinically important than its gene-regulatory effects.

Multiple mechanisms are a strength in theory, but they also make it harder to predict which effects will dominate in humans.

3. Brain Health and Neuroprotection

Fisetin has been studied extensively in models of cognitive ageing and neurodegeneration:

• Memory and synaptic plasticity: work from the Maher lab at the Salk Institute showed fisetin improved memory, reduced neuroinflammation and maintained synaptic proteins in aged Alzheimer's model mice.
• Stroke and ischaemia: animal studies report reduced infarct size and improved recovery when fisetin is given after cerebral ischaemia, linked to Nrf2 and anti-inflammatory pathways.
• Dementia risk factors: a 2024 review in Phytomedicine summarised evidence that fisetin can reduce multiple physiological risk factors for dementia, including oxidative stress, neuroinflammation and vascular dysfunction (ScienceDirect).
• CMS121: a fisetin derivative, CMS121, is being developed for Alzheimer's disease. A 2025 phase I preprint reported acceptable safety, pharmacokinetics and cardiodynamics in healthy volunteers (medRxiv).

4. Cardiovascular and Vascular Function

Endothelial dysfunction — stiffening and reduced nitric-oxide signalling in blood vessels — is one of the earliest features of vascular ageing. Fisetin is being tested directly in this area:

• University of Colorado Boulder trial (NCT06133634): "Clinical Translation of Senolytic Therapy With Fisetin to Improve Vascular Function in Older Adults" is a randomised, double-blind, placebo-controlled study testing intermittent fisetin on endothelial function in older adults.
• Preliminary mechanistic work: a 2026 abstract in Physiology reported that intermittent fisetin improved vascular endothelial function and suppressed cellular senescence in older adults, partly through reduced mitochondria-related oxidative stress (doi:10.1152/physiol.2026.41.s1.2277288).
• Peripheral artery disease (NCT06399809): the FIRST pilot trial is testing whether fisetin reduces senescence and improves walking ability in people with PAD.

These vascular trials are among the most important for longevity, because cardiovascular disease remains the leading cause of death and disability in older age.

5. Skin Ageing and Photoaging

Skin is the most visible ageing tissue, and fisetin has been studied in several dermatology models:

• UVB protection: fisetin reduced UVB-induced inflammation, oxidative stress and matrix metalloproteinase (MMP) activity in hairless mice, helping preserve collagen structure (PMC4294956).
• UVA protection: in human dermal fibroblasts and keratinocytes, fisetin inhibited UVA-induced MMP-1 and MMP-3 expression through the NOX/ROS/MAPK pathway, suggesting a collagen-preserving effect (doi:10.3390/ijms242417358).
• Nrf2 pathway in skin: a 2017 study showed fisetin regulated Nrf2 expression and inflammation-related signalling to prevent UVB-induced skin damage (doi:10.3390/ijms18102118).
• Topical delivery: a 2025 formulation study used ascorbyl palmitate/hyaluronan-enhanced liposomes to improve topical fisetin delivery for preventing UVB-induced photoaging (Journal of Drug Targeting).

Human clinical trials of topical or oral fisetin for skin rejuvenation remain limited. The published work is primarily preclinical.

6. Metabolic Health and Inflammation

Ageing is accompanied by low-grade, chronic inflammation and insulin resistance. Fisetin has been studied in several metabolic models:

• Obesity and diabetes: animal studies report improved glucose tolerance, reduced fat accumulation and lower inflammatory markers in high-fat-diet models.
• Biological-age markers: a 2024 article in Alternative Therapies discussed the effects of fisetin on reducing biological ageing, citing improvements in oxidative stress and inflammatory markers (Alternative Therapies, Sept 2024).
• Polyphenol review: a 2024 Nutrients review on dietary polyphenols as anti-aging agents highlighted fisetin as one of several compounds targeting hallmarks of ageing including oxidative stress and inflammation (doi:10.3390/nu16193305).

Again, the metabolic evidence is mainly from cells and animals. Human metabolic trials with fisetin are still in early stages.

7. Human Trial Landscape in 2025–2026

Several registered trials are now moving fisetin from mice to people:

• NCT07195318: "Fisetin Supplementation for Healthy Aging" — a 120-participant trial led by Ove Andersen, recruiting from September 2025, expected to complete October 2026.
• NCT06133634: Colorado Boulder vascular function trial in older adults — active, not recruiting as of late 2025.
• NCT06399809 (FIRST): fisetin to reduce senescence and mobility impairment in peripheral artery disease — recruiting.
• NCT06796374 (FISEKIN-1): comparison of fisetin pharmacokinetics in young and old adults — recruiting.
• NCT07279714 (FIS-AD): pilot trial of fisetin in mild Alzheimer's disease — recruiting.
• NCT07676435: Cedars-Sinai phase II pilot of fisetin for lung decline with age — recruiting.
• TROFFi (NCT05415037): phase II randomised trial of fisetin to improve physical function in breast cancer survivors; design published in 2026 (Therapeutic Advances in Medical Oncology).

8. Safety, Dosing and Buying in the UK

What doses are used?

The most-discussed human protocol comes from Mayo Clinic senolytic trials: intermittent high-dose fisetin on two consecutive days per month, repeated monthly. For a 70 kg adult this equates to roughly 1,000–1,400 mg/day on dosing days, with no daily low-dose use between cycles. This is an experimental protocol, not an established supplement regimen.

UK food supplements typically contain 100–500 mg/day capsules. These are far below trial intermittent doses and have not been proven senolytic.

Safety considerations

• Short-term safety data from Mayo Clinic-style studies are reassuring, but long-term safety in healthy adults is unknown.
• Fisetin may have antiplatelet effects; use caution with warfarin, apixaban, rivaroxaban, clopidogrel and aspirin.
• Theoretical concern with chemotherapy and radiation; do not use without oncology advice.
• Avoid in pregnancy and breastfeeding; no safety data.
• Stop high-dose fisetin before surgery due to bleeding risk.

Buying tips

If you and a clinician decide to try fisetin, look for high-purity extracts (often 98%+ from Sophora japonica), third-party certificates of analysis, and a UK-registered seller. Read our dedicated fisetin senolytic guide for more detail on products and protocols.

9. References

10. FAQ