Fisetin Effectively Eliminates Senescent Cells and Restores Stem Cells

Fisetin is a flavonoid found in fruits and vegetables and has been shown to have powerful senolytic properties.  In a new study, fisetin was shown to prevent immune cells from becoming senescent, allowing them to enter into a state of apoptosis or cellular suicide, a normal process at the end of a cell’s life cycle. The dosage used for mice was 20 mg/kg for 5 consecutive days each week for 4 weeks.

Immune cells clear away senescent cells

Immune cells, also called macrophages, are responsible for removing senescent cells that accumulate in the body.

“In normal conditions, senescent cells accumulated in body are specifically identified and removed by immune system” (1)

Aging Immune cells lose their ability to clear away senescent cells

The study showed that over time, aging or diseased macrophages lose their ability to clear senescent cells, leading to their accumulation and contributing to age-related disorders.

“when the immune cell become senescent too, their ability to clear senescent cells would be greatly compromised, leading to excessive accumulation of senescent cells and aging-related disorders” (1)

Figure 1. muscle exhibits obvious stem cell exhaustion, immune cell infiltration and cellular senescence

Senescent cells a key target for new senolytic drugs

In addition to losing their ability to clear away senescent cells, macrophages also begin to release what are known as SASP factors into surrounding tissues, causing them to become senescent as well.  This is why senescent cells are often referred to as “zombie cells” and are considered a key target for senolytic therapy.

“the ageing immune system, or immunosenescence, has a causal role in driving systemic ageing and therefore represents a key therapeutic target to delay ageing” (1)

Senolytics has arisen as a novel anti-aging strategy

Research has shown that removal of senescent cells can prevent many age-related diseases and delay the aging process in animals.  This is why so much new research has gone into finding the best approach to ridding the body of these cells.

“elimination of senescent cells with senolytic drugs (senolytics) have arisen as a novel anti-aging strategy and therapeutic approach for treating many age-related diseases” (1)

Fisetin eliminates senescent cells by targeting critical signaling pathway

Cells can become senescent by receiving signals that prevent them from going into apoptosis, a type of cellular suicide at the end of a cell’s life.  Fisetin interferes with this signaling pathway, allowing the cell to die and be swept away so that new stem cells can take its place.

“Senolytics can selectively eliminate senescent cells by targeting anti-apoptotic signaling pathways that are overtly upregulated in senescent cells” (1)

“the elimination of senescent macrophages with fisetin is able to rescue the function of MPCs” (1)

Figure 2. Fisetin treatment specifically remove senescent macrophages

Weekly administration of fisetin effective in eliminating new senescent cells

After initial treatment with fisetin and the successful removal of senescent cells, it was discovered that within weeks, senescent cells began to reaccumulate.  By administering fisetin on a weekly basis, though researchers were able to eliminate accumulation of new senescent cells and allow new stem cells to continue to form.

“Because senescent cell usually takes weeks to reaccumulate, intermit administration of senolytics is efficient to achieve ideal results” (1)

“weekly administration of fisetin in mice is effective in eliminating many of senescent cells and rescue the growth and function of MPCs” (1)

Fisetin removes and prevents immune cells from becoming senescent

Since immune cells play such a critical role in keeping the population of senescent cells in check, senescent immune cells are a prime target of senolytic drugs.  Fisetin has been shown to be an effective in both the removal of senescent immune cells and the promotion of new stem cells.



1 – Senolytic elimination of senescent macrophages restores muscle stem cell function in severely dystrophic muscle