Cell Senescence and Aging
Quercetin & Dasatinib
When we are young, cells naturally eliminate themselves if they become damaged or dysfunctional. This process is known as apoptosis, where damaged (senescent) cells shut off. This self-elimination is a normal and important part of maintaining and regenerating healthy tissues. As organs age, more and more cells become senescent.
These zombie-like cells emit harmful compounds that promote inflammation in the surrounding tissue. Chronic inflammation is a major contributor to degenerative disorders. Published research demonstrates that a buildup of senescent cells leads to the acceleration of our body’s aging process, which increases the risk of age-related diseases. Diabetes, vision loss, stroke, obesity, emphysema, osteoarthritis, neurogenerative disorders, and cancer could be connected to the presence of senescent cells.
The possibility of removing senescent cells from our body provides an innovative approach to modulating and reducing the cellular factors of aging. Just 1 senescent cell out of 7,000 to 15,000 healthy cells can initiate degenerative aging. To make matters worse senescent cells appear to pass on their age-accelerating toxicity to normal cells, thus creating a spiral of pathologic disorders that result in chronic illnesses and premature death.
What are Senescent cells?
- Damaged cells that lose the ability to properly function
- They linger in a zombie-like state, not fully alive, and not fully dead
- Senescent cells accumulate and inflict systemic damage by
- emitting pro-inflammatory signals
- secreting protein-degrading enzymes
Mayo Clinic and the Scripps Research Institute are researching these cells and testing compounds to target and eliminate these zombie cells. Listed below are some of the compounds being tested:
What are Senolytics?
Senolytic compounds can be drugs, peptides, or plant extracts that act to cleanse the body of senescent cells. In human cell and animal studies, consistent findings show that removing senescent cells from the body improves various markers of aging and prolongs lifespan in some models.
In a 2016 SCIENCE study, researchers demonstrated that in a mouse model of atherosclerosis, removal of senescent cells led to significant inhibition of growth and even regression of arterial plaque. This ability to block or reverse plaque could be an important step in preventing heart and blood vessel disease.
In another study published in NATURE, a mouse aging model demonstrated that removing senescent cells benefited multiple tissues while delaying the onset and slowing the progression of age-related disorders.
How do Senolytics work?
Senescent cells fail to undergo programmed seld-elimination. Like a contagion, senescent cells pass on their accelerated aging properties to healthy cells by releasing a number of factors that can cause tissues to deteriorate.
Senolytic compounds target anti-apoptotic pathways that cause senescent cells to self-destruct and help eliminate them from the body. Senolytics are able to specifically target these cells and activate their suicide switch so that they proceed to die a normal death. This allows toxic cells to be removed from the body without harming highly functioning, healthy cells.
Quercetin is a compound in many fruits and vegetables with multiple health benefits.
- an anti-inflammatory agent that protects cells and tissues from injury
- demonstrated to improve markers of aging and extend lifespan in lab studies
- demonstrated to reduce or prevent age-related disease and dysfunction in humans
Quercetin can clear senescent cells from tissues when combined with other compounds. Quercetin acts as a senolytic and can enable a rejuvenating effect in healthy cells.
- Cellular senescence increases in our tissues as we age
- The presence of senescent cells is associated with the progression of age-related loss of function and the development of age-related disease
- Reducing the senescent cell burden in our tissues may help maintain optimal function and reduce the risk for disease
- Natural compounds have demonstrated senolytic activity in animal studies, and the ability to improve markers of health in humans
- Incorporation of quercetin into phytosomes improves quercetin bioavailability. The combination with theaflavins could prove an effective senolytic cocktail
Quercetin can have a low bioavailability, so researchers integrated it into a phytosome to improve quercetin's absorbability in humans. Phytosomes combine a natural compound with a plant-based phospholipid carrier. This enables much more quercetin to enter the bloodstream to exert its beneficial effects throughout the body.
Research led by the Mayo Clinic and Scripps Research Institute scientists used quercetin along with a chemotherapeutic drug, dasatinib, in their studies. They demonstrated that quercetin along with dasatinib removed human senescent cells from cell cultures to a greater degree than either compound alone.
When dasatinib and quercetin were administered to old mice, systematic regeneration occurred. Dasatinib is a drug intended to treat cancer, but also seems to have rejuvenation potential when paired with quercetin. Theaflavins are compounds that exhibit senolytic-like effects and similar mechanisms of action, which can be found naturally in black tea.
Theaflavins have exhibited numerous health benefits, including lifespan extension
Most excitingly, theaflavins demonstrated senolytic-like effects in a recent animal study. Theaflavins are safe and free of the side effects that can occur with dasatinib. The combination of quercetin and theaflavins pack a senolytic punch, without side effect concerns.
The Mayo Clinic and Scripps Research Institute also uncovered that intermittent dosing of quercetin and dasatinib improved grip strength, coast condition, movement, and overall health. The Mayo Clinic study also revealed improvement in a biomarker of senescent cells in the kidney compared with control mice. These results suggest that combinations of natural senolytics such as quercetin phytosome and theaflavins may also restore youthful cellular function, even when taken on an intermittent basis.
In summary, cell senescence is common in aged tissues. Senescent cells cannot remove themselves from the body through normal channels. Their impairment and tendency to promote inflammation contribute to loss of physical function and the risk for age-related disease and disability. Senolytic compounds have the ability to cleanse the body of these cells, improving organ function and preventing disease. Several compounds are being actively studied for these effects and to define their optimal role in promoting longevity.
Quercetin and theaflavins have a number of different properties that promote health and longevity, including senolytic activity. Delivery of quercetin in a phytosome and co-administrating it with theaflavins may help maximize the senolytic effect. Stay tuned for more content regarding these fascinating findings and please share any new research you come across on this topic.