About Senescent Cells
Senescent cells are cells that have reached a state of permanent cell cycle arrest, meaning they can no longer divide, but they do not die off; instead, they remain alive and can release chemicals that may damage nearby healthy cells, often contributing to the aging process and age-related diseases; essentially, they are "zombie cells" that continue to exist and can have negative effects on surrounding tissues.
Aging leads to a sharp decline in immune function, precipitating the development of inflammatory conditions.
"As we age we are at greater risk of inflammatory and immune-related diseases, such as cancer and infections. This state of diminished cellular function is driven by cellular senescence"
Reference
With aging, we accumulate too many of these malfunctioning (senescent) cells that refuse to die. Sometimes referred to as “zombie cells,” they pump out toxic compounds that degrade nearby cells and incite chronic inflammation and/or silent inflammation that inflicts systemic damage.1
About Senolitic Activator
Our Senolytic Activator® (for people 45 and older) combines black tea theaflavins, the plant-derived flavonoid apigenin, and ultra-absorbable forms of the bio-flavonoids quercetin and fisetin to help manage senescent cell burden and promote systemic rejuvenation.
Clinical research on dosing protocols is still in its early stages, but current studies suggest that senolytics may not require daily usage.
The plant flavonoid fisetin is currently considered one of the most powerful natural senolytics.4,6-20Enlightened individuals today are taking this highly absorbable fisetin by itself and/or combining it with a once-weekly high potency quercetin + theaflavins for enhanced senolytic effects.
In youth, cells naturally eliminate themselves if they become damaged or dysfunctional. This process is called apoptosis.
With age, however, we accumulate more senescent cells that emit toxic byproducts, that cause more cells to become senescent. These dysfunctional cells no longer perform basic functions. They instead inflict localized and systemic damage to our healthy cells.
Senescent cells undergo a series of trans-formations that result in their secreting high levels of toxic compounds, collectively referred to as SASP or senescence-associated secretory phenotype.
As a result, the buildup of senescent cells has been shown to accelerate the aging process and increase the risk of age-related diseases, including:23-30- Diabetes,
- Obesity,
- Stroke,
- Vision loss,
- Neurodegenerative disorders,
- Osteoarthritis,
- Emphysema, and
- Cancer.
Research shows that just one senescent cell out of 7,000-15,000 healthy cells can initiate degenerative aging.31
The effects of fisetin go beyond its potent senolytic activity.
Fisetin also:
- Protects the brain in various models of neurodegenerative disorders,6-8,13-15,20
- Improves outcomes in people who have suffered strokes,18
- Helps prevent malignant changes inside cells, 11,12
- In animal and experimental models, helps fight obesity and type II diabetes tendencies,9,10
- Reduces the risk of atrial fibrillation after a heart attack, in an animal study,38
- Reduces levels of pro-inflammatory mediators, in a study of colorectal patients,39 and
- Based on results of preclinical studies, may inhibit cancer migration and growth and incite cancer cell death.16,40-45
Fisetin also has an ability to impact many of the same cellular pathways that calorie restriction does.2,15, Reducing food intake through a calorie-restricted diet has been shown to slow aging, extend lifespan, and improve resistance to disease.48
What You Also Need To Remember
- As cells age and accumulate damage, they can enter a state known as cellular senescence. Senescent cells can cause dysfunction and damage throughout the body.
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Senescent cells are a major driver of aging and the development of many age-related chronic diseases.
- Recent research has confirmed that cellular senescence also affects the cells of the brain, including neurons.
- Studies have shown that senescent cells contribute to brain aging and the progression of neurodegenerative disorders like Alzheimer’s disease.
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Senolytics are compounds that are capable of eliminating senescent cells, rejuvenating tissues and improving their function.
- In animal models, senolytic therapy reverses the pathology associated with neurodegenerative disease and improves cognitive function.
References
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- Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. 2018 Oct;36:18-28.
- Zhu Y, Doornebal EJ, Pirtskhalava T, et al. New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Aging (Albany NY).2017 Mar 8;9(3):955-63.
- Ahmad A, Ali T, Park HY, et al. Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice. Mol Neurobiol.2017 Apr;54(3):2269-85.
- Alikatte K, Palle S, Rajendra Kumar J, et al. Fisetin Improved Rotenone-Induced Behavioral Deficits, Oxidative Changes, and Mitochondrial Dysfunctions in Rat Model of Parkinson’s Disease. J Diet Suppl.2021 Jan 29;18(1):57-71.
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- A cross over pilot pharmacokinetic study of fisetin 1000mg and formulated fisetin 200mg administered in a single dose to healthy volunteers. Manufacturer’s study (in press for future publication).2020.
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