All of the cells in our bodies are continuously renewing themselves. Older cells are aging and dying; at the same time, new cells are being generated. Sometimes this process can go wrong, and some cells become damaged and remain. These damaged cells are called senescent cells and they can have a negative influence on the other nearby cells. This changes how the neighboring cells handle inflammation, sugars or proteins, and can cause metabolic problems as well as lead to multiple age-related chronic diseases.
What are Senolytics?
Senolytics are a class of drugs, supplements or peptides that can help eliminate senescent cells. They do this by disabling the mechanism by which these senescent cells survive.
Senescent cells can build up in different tissues. Aging is the main reason they accumulate, but they are also present in obesity and metabolic diseases. These cells can cause dysfunction and secrete inflammatory cytokines, chemokines, and proteases, termed the senescence-associated secretory phenotype (SASP).
Ongoing research in humans and animals has shown that by using Senolytics we can help eliminate these problem-causing cells.
In simple terms, treatment with senolytic agents can alleviate metabolic and adipose tissue dysfunction and inflammation.
The first senolytic drugs—Dasatinib, Quercetin, Rapamycin, Fisetin and Navitoclax—were discovered using a hypothesis-driven approach.
Dasatinib is a cancer drug, sold under the name Sprycel to treat certain types of leukemia in adults and children. It induces apoptosis in senescent cells by inhibiting the Src tyrosine kinase, while quercetin does so by inhibiting the anti-apoptotic protein Bcl-xL.
Quercetin is a naturally occurring flavonoid with antioxidant and anti-inflammatory activity. It is sold as a nutritional supplement. This drug combination targets and eliminates senescent cells that are linked to multiple age-related chronic diseases.
Dasatinib & Quercetin Research
Some of the preliminary research showed that dasatinib and quercetin reduced adipose tissue senescent cell burden within 11 days, with decreases in cellular senescence markers, decrease in cells with senescence-associated β-galactosidase activity, and adipocyte progenitors (similar to stem cells). Adipose tissue macrophages (which are attracted, anchored, and activated by senescent cells) were also decreased. Skin epidermal senescent cells were reduced, as were circulating SASP factors, including interleukin 1α & 6, and Matrix metalloproteinases 9 & 12.
Other trials of senolytics suggest they can decrease senescent cells, reduce inflammation and alleviate frailty in humans. Clinical trials are underway for diabetes, eye diseases, metabolic and skin disorders, Alzheimer's disease, cardiovascular, liver, kidney and lung diseases, osteoarthritis, COVID-19, osteoporosis and bone marrow transplant and childhood cancer survivors.
The senolytic combination of Dasatinib and Quercetin are given intermittently in a ‘hit-and-run’ fashion, meaning they aren’t taken daily. Both of these are effective at reducing senescent cell burden. There are less side effects associated with this type of therapy because dosing is intermittent.
Potential Benefits of Dasatinib & Quercetin
- May improve senescent cell markers
- May slow cell proliferation and decelerate aging and the risk of age-related diseases
- May lessen age-dependent disc degeneration
- May improve metabolic disease
- May improve effects of diabetes (improved glucose tolerance & insulin sensitivity)
- May lower circulating inflammatory mediators, and promoted adipogenesis
- May improve neurodegeneration
Dasatinib may cause low blood cell counts, anemia, rash, and diarrhea. It may also cause serious side effects such as bleeding, pulmonary edema, heart failure, and prolonged QT syndrome. These potential side effects are more common when dasatinib is used daily.
The Safety and Effectiveness of Quercetin and Dasatinib on the Epigenetic Aging Rates in Healthy Individuals. Start Date Dec 16th 2020, Primary completion Dec 31 2021, Study Completion June 30 2022
Another clinical study is underway to evaluate the effectiveness of Quercetin and Dasatinib supplements on the patient's epigenetic aging rate. The investigators predict that Quercetin and Dasatinib combined will slow cell proliferation and thus decelerate the rate of aging.
The Translational Geroscience Network, headed by the Kirkland team at the Mayo Clinic is conducting senolytic clinical trials targeting fundamental aging mechanisms to extend health span and delay, prevent, or treat age- and cellular senescence-related conditions.
The findings from all these trials will help determine and confirm the safety and efficacy of natural and prescription senolytics. They will also help in the development of treatment protocols for patients with multiple chronic diseases. We know that aging mechanisms are the root cause of multiple disorders. It is exciting to see the potential uses of senolytics in potentially alleviating over 40 age-related dysfunctions and diseases.
The rationale for so-called “senolytic therapy” for AD arises from studies implicating senescent glia and neurons in neurodegeneration due to tau or amyloid pathology (Sep 2018 news).
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