What is Fisetin?

Fisetin is a plant flavonol (a type of polyphenol) found in small amounts in several fruits and vegetables, including strawberries, apples, onions, grapes, and cucumbers. It has attracted interest in aging research because preclinical studies (cell and animal) show fisetin has antioxidant activity and can modulate inflammatory signaling, stress-response pathways, and markers associated with cellular senescence. Preclinical mouse studies also report improved measures of health and lifespan extension when fisetin is given later in life. However, these findings are primarily preclinical, and it is not yet established that fisetin clears senescent cells or produces longevity benefits in humans.

Fisetin Anti-Aging Impacts Aging Via

• Cellular senescence
• Altered intercellular communication
• Loss of proteostasis
• Nutrient-sensing/metabolic signaling
• Cell-cycle and apoptosis-related gene programs

Exploring the connection between fisetin and our golden years.

Fisetin is a flavonoid, a broad class of plant polyphenols. Flavonoids include many compounds that help plants respond to environmental stress, and some also contribute to the bright colors of fruits and vegetables. In human biology, flavonoids are studied not only for antioxidant activity in laboratory settings, but also because they can influence cellular signaling pathways involved in stress responses and inflammation.

The importance of fisetin supplements lies in their dosage and bioavailability. Like many polyphenols, fisetin has low water solubility and is extensively metabolized after oral intake, which can limit absorption. Taking fisetin with a meal, especially one that contains dietary fat, may help improve absorption.

Fisetin and senescent cells

Fisetin is widely studied for its effects on cellular senescence, a process in which damaged cells permanently stop dividing but do not undergo programmed cell death. Senescent cells accumulate in many tissues with age and contribute to age-related dysfunction.

Unlike most damaged cells that are removed, senescent cells can linger. They release many chemical signals, often called the SASP, that can drive inflammation, weaken the tissue “scaffolding” around cells, and interfere with the function of nearby healthy cells.

Preclinical studies (cell and animal models) suggest that fisetin can reduce markers of senescent cell burden and modulate senescence-associated signaling in certain tissues. Through these effects, fisetin has been associated with reduced inflammation-related signaling and improved tissue function in aging models. However, it has not been established that fisetin selectively clears senescent cells or produces senolytic effects in humans (R).

Senescent cells are also known to interfere with stem cell function, limiting the body’s ability to repair and regenerate tissues. In animal models, reducing senescence-associated signaling has been linked to improvements in stem cell activity and tissue maintenance, though the relevance of these findings to human aging remains under investigation.

Compounds that can selectively target senescent cells are referred to as senolytics. Fisetin is best described as a senotherapeutic candidate with senolytic-like effects reported in preclinical research. While fisetin has demonstrated cytotoxic effects in cancer cell lines in laboratory studies, these findings do not establish cancer prevention or treatment effects in humans (R).

 

Fisetin versus quercetin

Fisetin and quercetin are naturally occurring flavonoids that have been studied for their effects on cellular senescence in preclinical research. Although they share some structural similarities, their biological effects can differ depending on the cell type, dose, and experimental model.

In a cell-based screening experiment, fisetin showed the strongest reduction in senescent cells among the compounds tested, including quercetin, curcumin, and EGCG (R):

In this assay, fisetin reduced the relative number of senescent cells more than any other compound, while having a comparatively smaller effect on total cell number. This profile suggests a more pronounced senotherapeutic effect under the specific conditions of the experiment.

These results come from in vitro studies and reflect outcomes in cultured cells under controlled conditions. While they do not establish effects in humans, they clearly highlight fisetin as a leading compound in this experimental comparison, which is why it has received significant attention in aging research.

Lifespan extension benefits of fisetin

Fisetin has been evaluated in several well-established lifespan models, where it has been shown to extend lifespan under specific experimental conditions. Across these studies, fisetin increased lifespan in evolutionarily diverse organisms, supporting its relevance in aging research.

In yeast (Saccharomyces cerevisiae), fisetin increased replicative lifespan by approximately 55%, as reported in early longevity studies (R). In fruit flies (Drosophila melanogaster), fisetin supplementation extended lifespan by about 23% (R). In nematodes (Caenorhabditis elegans), fisetin increased mean lifespan by approximately 10%, based on reported survival data (R).

In mice (Mus musculus), fisetin supplementation initiated late in life significantly extended lifespan. In a well-characterized mouse study, fisetin increased median lifespan by approximately ~17%, as quantified by the DrugAge database based on the published survival curves and statistical analyses from the original study. This finding is notable because the intervention began at an advanced age, demonstrating that fisetin can influence survival even when introduced late in the lifespan (R).

More than a senolytic: other anti-aging and fisetin skin benefits

Fisetin has been studied for more than just senescence-related biology. In preclinical research, fisetin has also been linked to pathways involved in inflammation, oxidative stress, and cell signaling that become dysregulated with age. (R)

Inflammation

In multiple laboratory studies, fisetin has been shown to dial down inflammatory signaling, including effects on a key inflammation “switch” called NF-κB, and to reduce the production of inflammatory messengers in experimental models (R ,R)

Oxidative stress

Fisetin is also studied for its ability to help cells handle oxidative stress. In cell models (including nerve-cell–relevant systems), fisetin supported natural antioxidant defenses, such as increasing glutathione, one of the body’s major internal antioxidants, and helped protect cells under stress conditions (R).

Cell growth and metabolism signaling

Finally, fisetin has been studied in pathways that control cell growth and metabolism. In certain cell studies, fisetin affected Akt/mTOR-related signaling, a set of pathways often discussed in aging biology because they help regulate growth, nutrient sensing, and stress responses (R, R).

NOVOS CORE & Fisetin