Fisetin and Longevity

Fisetin Impacts Aging Via

• Cellular senescence
• Altered intercellular communication
• Loss of proteostasis

The role of fisetin in aging and longevity

Fisetin is a naturally occurring substance found in fruits and vegetables, such as strawberries, apples, grapes, onions, and cucumbers. 

Fisetin is a flavonoid. Flavonoids are substances that give fruits and vegetables their bright colors (like yellow, orange and blue) and play a major role in conferring the health benefits that we get from eating more vegetables and fruits.

Fisetin eliminates senescent cells

Fisetin is probably most known for its impact on senescent cells: studies showed that this substance can reduce the accumulation of senescent cells (R). Fisetin is a senolytic, a compound that can clear away senescent cells. 

Senescent cells accumulate everywhere in the body during aging.

Senescent cells were previously normal cells that became too damaged. Normally, when a cell is too damaged, it kills itself, but senescent cells don’t do that.

Instead of dying, they keep lingering around in the body; a zombie cell, so to speak. 

Senescent cells secrete all kinds of substances that damage the healthy surrounding cells, like inflammatory substances (cytokines and chemokines), substances that break down the glue that holds the cells together (matrix metalloproteinases), and growth factors that accelerate aging (R). 

Senescent cells play a considerable role in the aging process.

Not only do senescent cells damage healthy surrounding cells, but they also damage stem cells, which are the foundational cells that create new cells, which build up and repair our organs and tissues.

Reducing the senescent cell burden can lead to reduced inflammaging (low-grade inflammation that increases during aging) and enhanced function of stem cells.

Substances that can eliminate senescent cells are called “senolytics”. Fisetin is a well-studied senolytic substance.

Fisetin versus quercetin

Besides fisetin, another senolytic is quercetin. Quercetin and fisetin look very similar. However, fisetin seems to be the most potent and safest of natural senolytics (R):

The conclusion of the researchers was the following:

“Fisetin had the most potent senotherapeutic effects in several cell types in vitro and showed strong anti-geronic effects in vivo”.

Lifespan extension effects of fisetin

Scientists demonstrated that fisetin can extend median and maximum lifespan in mice, even when taken late in a mouse’s life (equivalent to 50 or 60 years old for a human) (R): 

Another study showed that fisetin reduced the impact of aging in a mouse model of accelerated aging.

Old mice receiving fisetin were better in navigating a maze and in recognizing objects, which translates into improved cognition and memory:

More than a senolytic: other anti-aging effects of fisetin

Fisetin has many other beneficial effects on the aging process besides eliminating senescent cells. 

For example, fisetin inhibits the mTOR pathway (R), which plays an important role in aging and is where many of the health benefits behind fasting are derived. Fisetin can also reduce oxidative stress (R).

Fisetin can reduce inflammaging (aging-related low-grade inflammation) by inhibiting pro-inflammatory enzymes and substances, like lipoxygenases and NF-kB (R,R). 

Interestingly, fisetin can also have various beneficial effects on the skin. For example, fisetin can reduce the formation of skin wrinkles and appearance of skin aging.

One way it can achieve this is by reducing the amount of matrix metalloproteinases (MMPs) (R,R). MMPs are enzymes that break down the extracellular matrix that surrounds our cells. The extracellular matrix consists of collagen, elastin, hyaluronic acid, glycosaminoglycans (GAGs), and many other molecules that glue the cells together, so that they can firm tissues (like the skin) and organs. An overactivity or overproduction of matrix metalloproteinases plays a role in wrinkle formation.

Fisetin also has a positive impact on brain functioning and brain aging (R). For example, fisetin can improve memory formation in mice (R,R). 

NOVOS contains 100 mg of fisetin per sachet.