Senolytics Offer New Hope for Heart Failure

Heart failure occurs when the heart is unable to pump enough blood to fully oxygenate the body.

As it progresses, heart failure patients may lose the ability to walk, speak, or carry out basic activities without pausing for breath or stopping to rest.

In advanced stages, vital organs stop functioning. Unless the clinical course of chronic heart failure is reversed, death ensues.

According to a 2020 report by the American Heart Association, one million new heart failure cases are diagnosed in the U.S. each year.¹

Heart failure is associated with a cumulative burden of senescent cells that don’t function normally. Instead, senescent cells emit pro-inflammatory and protein-degrading factors that damage healthy heart cells.

In a compelling study, researchers found that the senolytic cocktail of dasatinib + quercetin cleared senescent cells effectively in lab cultures of human senescent heart tissue and promoted survival of crucial cardiac progenitor cells.²

Senolytics are a promising therapy that may allow the heart to heal itself.

Old, dysfunctional senescent cells contribute to heart failure and prevent damaged heart tissue from healing.^2,3

Among people older than 70 with cardiovascular disease, more than half of cardiac progenitor cells—cells capable of producing fresh, new heart muscle tissue—are senescent.²

In recent years, anti-aging research has increasingly focused on compounds called senolytics that remove senescent cells while leaving healthy cells to flourish.

Many age-related diseases are associated with an accruing senescent cell burden.^4-6

These aged, damaged cells accumulate in our tissues, refusing to die off. They instead secrete inflammatory molecules that damage surrounding healthy cells.

Within the last few years, scientists have discovered that compounds called senolytics have the power to selectively trigger senescent cells to self-destruct, while leaving most normal cells unharmed.

Using senolytics to eliminate those “zombie” cells improves health and extends life in animals.⁷

Decreasing the senescent cell burden has been shown to:

• Reduce glucose levels, raise insulin sensitivity, lower inflammation, and improve kidney and heart function in obese mice,⁸
• Restore memory loss in a mouse model of Alzheimer’s disease and decrease the toxic proteins that make up the amyloid plaques found in the brains of Alzheimer’s patients,⁹
• Increase lifespan, promote youthful body type, and reduce age-related diseases in mice, and¹⁰
• Reverse age-related damage to heart muscle, including stiffening and over-growth of tissue, in aged mice.¹¹

Senolytics were initially studied in animals or lab cultures.

Recent human studies on the experimental senolytic cocktail—dasatinib and quercetin—have shown some early promise as an effective clinical therapy.

Dasatinib is a prescription drug developed to treat certain forms of leukemia.¹²

It is on the latest report of the World Health Organization’s Model List of Essential Medicines.¹³

Quercetin is a bioflavonoid found in apples, honey, berries, onions, red grapes, cherries, citrus fruits, green leafy vegetables, tea, and other food sources.¹⁴

The combination of these two compounds has been used as senolytic therapy to eliminate senescent cells in multiple animal and lab studies.¹⁵

Scientists expanded this research into patients with idiopathic pulmonary fibrosis. This progressive lung disease, once diagnosed, carries a median survival of 3.8 years in adults aged 65 and over.¹⁶

Cellular senescence has been identified as a major contributing factor to this disease.

In a three-week study, 100 mg/day dasatinib and 1,250 mg/day quercetin, taken three consecutive days per week for three weeks, improved:¹⁵

• Distance walked in six minutes,
• Speed of gait in a four-meter walk, and
• Time to complete five consecutive stand-up/sit-down cycles on a chair.

None of the subjects experienced adverse effects requiring discontinuation of treatment.¹⁵

Though it was a preliminary study, it showed that the dasatinib-quercetin cocktail may have a positive impact on health.

Intriguing evidence that senescent cells are involved in cardiovascular disease has led scientists to look for ways to use senolytics to clear out those cells from heart muscle and restore youthful heart function.

In a compelling study, researchers from Kings College London and the Mayo Clinic tested the dasatinib-quercetin combination in lab cultures of human senescent heart tissue.²

The combination not only cleared senescent cells effectively, but also promoted survival of crucial cardiac progenitor cells, those that produce fresh, new heart muscle tissue.²

The researchers also tested the dasatinib-quercetin cocktail in an animal model of age-related human heart failure.

Previous mouse studies showed that this combination led to decreased numbers of senescent cells in heart muscle, aorta, lung, liver, bone, fat, and skeletal muscle.²

The treated mice also showed a burst of growth of fresh, new heart muscle cells that was accompanied by a sharp decrease in fibrosis (stiffening and thickening) of the main pumping chamber of the heart.²

In other words, the dasatinib-quercetin combination effectively cleared out senescent heart muscle cells, showing great promise for the maintenance of a healthy heart function.

Chronic heart failure remains a major threat for older Americans.

We’ve recently learned that aging heart muscle, like other tissues, is riddled with old, damaged cells that weaken cardiac function and contribute to heart failure.

Multiple studies show that removing senescent cells can make room for healthy, tissue-healing cells to emerge and function normally.

Studies indicate that a combination of two compounds, the drug dasatinib and the plant pigment quercetin may be effective in treating people suffering chronic heart failure.

Clinical trials are urgently needed as over 80,000 Americans die each year of heart failure.¹

At this point, the dasatinib-quercetin combination is still experimental. Anyone who uses it should report results to Life Extension^® so we can include them in future issues.

Those concerned about taking a chemotherapy drug like dasatinib, even on the limited basis used in experimental research, have been using a black tea extract called theaflavins combined with high-dose quercetin on a once-weekly basis.Theaflavins function via some similar mechanisms as does dasatinib.^17,18

Even more exciting, anticipated later this year is the introduction of bioavailable fisetin, a plant extract that some scientists believe may be the most effective senolytic compound.¹⁹ •

If you have any questions on the scientific content of this article, please call a Life Extension^® Wellness Specialist at 1-866-864-3027.

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