Fisetin Benefits

Study Proven Benefits of Fisetin

Senolytics and Healthy Aging


Aging is the process of structural and functional changes accumulated as a result of the passage of time. The changes lead to impaired function and increased vulnerability to death.  The expansion of the global aging group makes aging not only a social issue but also a vital health concern.

Senolytics Effects on Healthy Aging

With age, an increasingly dysfunctional immune system contributes to an accumulation of senescent cells. Even a relatively low number of senescent cells are sufficient to cause chronic damage to healthy cells and the body, driving aging and age-related diseases. Senolytics are the ingredient that eliminate these zombie cells, and alleviate disease in numerous organs, improve physical and mental function and resilience.

Senescence-Centric View of Aging. Sourcre image: A Senescence-Centric View of Aging: Implications for Longevity and Disease.  Trends Cell Biol. 2020

Research found that fisetin significantly removed senescent cells when applied to human umbilical vein endothelial cells. Compared to other plant-derived senolytics, like quercetin, curcumin, resveratrol, fisetin is most effective at destroying senescent cells in animal models and human cell cultures. Fisetin reduced the most senescence in a subset of cells in murine and human adipose tissue when 10 flavonoids were tested.

Fisetin was the most potent senolytic of the 10 flavonoids tested. Source image: Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018

By removing senescent cells, there is a dramatic effect of lifespan in mice model. In the test, mice given fisetin lived an average of about 2.5 months longer, an almost 10% extension of lifespan, even when treatment was started at the human equivalent of 75 years of age.

Research also showed that oral administration of fisetin is effective in eliminating many senescent fibro-adipogenic progenitors and rescuing the growth and function of muscle cells, thus facilitating muscle regeneration.

And fisetin treatment reduced the number of senescent tubular epithelial cells and myofibroblasts, thus decreasing senescence-associated secretory phenotype (SASP) expression, and attenuating kidney fibrosis.


Fisetin, a well-rounded anti-aging ingredients

Besides the senolytic effect, fisetin acts on multiple anti-aging mechanisms to achieve a holistic aging rescue.

Activate sirtuins by caloric restriction mimetic

Sirtuin activator is regarded as a longevity-promoting compound via enhancing the reprogramming of somatic cells. Calorie restriction is the most successful intervention to activate the sirtuin and delay aging or the development of chronic disease connected with aging. Studies prove that fisetin is a potential caloric restriction mimetic that modulates ionic homeostasis in senescence-induced and naturally aged rats model.

Effective inhibitor of the mTOR pathways

mTOR is directly related to aging. The use of mTOR inhibitors has been proven to extend longevity in several animal models and to provide protection against the majority of age-associated illnesses. Fisetin is an effective inhibitor of the mTOR pathways, thus contributing to anti-aging mechanisms in humans.

Maintain the body’s glutathione (GSH) level

We all know that GSH and GSH-associated metabolism provide the major line of defense for the protection of cells from oxidative and other forms of toxic stress. Maintenance of GSH levels is developing as an important therapeutic target to reduce the impacts of aging. The research showed that fisetin not only increases basal levels of GSH but also maintains GSH levels under oxidative stress conditions. Oral administration of fisetin at 15 mg/kg could greatly reduce the loss of total GSH from both the cortex and hippocampus.

Promising Neuroprotection Effects


Fisetin possesses dramaic neurotrophic activity. Fisetin affects multiple pathways implicated in brain aging and age-associated neurological diseases. Multiple mechanisms of action have been reported through numerous animal and cell culture studies including maintenance of redox homeostasis, activating neurotrophic factor signaling pathways and inhibiting inflammatory responses. Fisetin can also enhance cognitive function and in some cases, modulate proteasome activity. Fisetin has the potential to act as a multi-factorial therapeutic for reducing the decline in brain function associated with age-associated neurological diseases.

Fisetin and Alzheimer’s disease(AD)

In an animal model of Alzheimer’s disease, early treatment with fisetin improved cognition and decreased soluble Aβ, it also decreased oxidative stress, increased synaptic density, and decreased astrocytic inflammation (Currais et al, 2014). Fisetin prevented the development of deficits in learning and memory through enhancing the phosphorylation of extracellular-signal related kinase. It also decreased the levels of p25 in AD mice. p25 overexpression has been known to be related to inflammation and astrogliosis and synaptic damage.

Fisetin and Depression

Although depression is not directly fatal, it is a major cause of disease-related disability. A recent study looked at the effects of fisetin in two rodent models of depression: the tail suspension test and the forced swim test. Oral administration of fisetin showed a dose dependent effect on immobility times in both tests with 20 mg/kg bw being the most effective dose at reducing immobility time. (Anderson RJ, 2001). Fisetin also appeared to modulate the noradrenergic system which may also contribute to its anti-depressive effects.

Mechanism of Action For Nuroprotection

Promotes Hair Growth


Undoubtedly, hair thinning has become the biggest health problem for today folks. It brings tremendous mental pressure and appearance anxiety. Finding an effective and long-term edible supplement has become an urgent need for many people.

One research found that fisetin blocks the anti-hair growth effects of dihydrotestosterone- the most potent hormone among the androgens.

Fisetin promotes hair growth by the same mechanism of action as Dutasteride, a drug already approved for the treatment of prostate enlargement and can help to prevent and slow down hair loss.

Subsequently, fisetin is a strong human telomerase reverse transcriptase (hTERT) augmenting compound and promotes hair growth of shaved skin in a study. The overexpression of TERT in the skin has a clear effect in promoting hair synthesis.

Nutrients 2021, 13, 2087. https://doi.org/ 10.3390/nu13062087

Fisetin, The All-In-One Supplement For Wellness

Weight management

Fisetin activities may help with weight control by increasing the activity of AMPK and inhabiting mTOR activity. Fisetin-supplemented diet could prevent weight gain even under a high-fat diet.

Reduce Impact of Diabetes

Peripheral nerve dysfunction in the form of diabetic neuropathy is a major complication of diabetes that has a significant impact on the quality of life.  fisetin was able to reduce the impact of diabetes on peripheral nerve function in this model.

Improves Bone Health

Fisetin promotes osteoblast differentiation and osteogenesis through GSK-3β phosphorylation at Ser9 and consequent β-catenin activation and could be used as an effective strategy to prevent bone resorption, inhibiting osteoporosis.

Besides, fisetin has been found to decrease cartilage destruction and subchondral bone plate thickness and relieved synovitis in mice osteoarthritis models by inhibiting the IL-1β-induced inflammatory response and ECM degradation through activating SIRT1 in human osteoarthritis chondrocytes.

Alleviates Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by the aberrant accumulation of extracellular matrix in the lung and deterioration of lung function. Both clinical observations and epidemiological investigations indicate that IPF is an aging-associated disease.

Currently, there is no cure for IPF, however, certain treatments may slow the progression of IPF and improve lung function. Studies showed fisetin treatment can maintain normal function of fibroblasts and improve pulmonary fibrosis, by activating AMPK and inhibiting NF-κB activity.

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