These drugs can boost the production of a vital protein, offering a promising defense against the effects of aging and age-related illnesses. Prolonging human lifespans is becoming increasingly feasible thanks to breakthroughs in cellular research. In the future, combating the effects of aging might involve something as simple as taking a pill. Scientists at the Mayo Clinic have made strides in this area by exploring the potential of senolytic drugs. Their research, published in eBioMedicine, highlights how these drugs can boost the production of a vital protein, offering a promising defense against the effects of aging and age-related illnesses. The findings are supported by experiments conducted on both mice and humans. Senolytics, developed at the Mayo Clinic, work by clearing the bloodstream of senescent, or “zombie,” cells.
These malfunctioning cells contribute to a range of diseases and accelerate the detrimental processes of aging. The study reveals that the elimination of senescent cells leads to a significant increase in the production of a protective protein known as a-klotho. What are zombie cells? Senescent cells, colloquially known as “zombie cells,” are cells within your body that stubbornly persist and do not die. Usually, a cell starts out as a healthy, functioning component of the body. However, it may encounter various stressors such as oxidative stress, a viral infection, or other factors. In response to this stress, the cell has three possible outcomes: undergo self-repair, undergo cell death, or transform into a senescent, or “zombie,” cell. While zombie cells may have some advantages, they are not entirely detrimental. A 2017 study indicates that cellular senescence, the process by which normal cells transform into zombie cells, can actually be a positive response to tumor development. Instead of uncontrollably multiplying and contributing to tumor formation, a cell will turn into a zombie cell and halt its growth. On the other hand, zombie cells can also have negative consequences in different situations. As we age, these zombie cells accumulate within our bodies.
This accumulation can impede the body’s ability to repair damaged tissue and may cause the release of harmful chemicals that affect nearby healthy cells. Research has connected the presence of zombie cells to numerous age-related diseases such as atherosclerosis (a type of heart disease), diabetes, and lung disease. The impact of senolytic drugs Senolytics (or senolytic drugs) are a specific class of drugs that help clear out zombie cells. “We show that there is an avenue for an orally active, small-molecule approach to increase this beneficial protein and also to amplify the action of senolytic drugs,” says James Kirkland, M.D., Ph.D., a Mayo Clinic internist and senior author of the study. The researchers first showed that senescent cells decrease levels of a-klotho in three types of human cells: umbilical vein endothelial cells, kidney cells and brain cells.
The researchers demonstrated that by using senolytics desatinib and quercetin in three different mouse models, a-klotho levels were increased. Following the administration of desatinib and quercetin in clinical trial participants with idiopathic pulmonary fibrosis, a-klotho levels were also found to increase. Yi Zhu, Ph.D., a Mayo Clinic physiologist and biomedical engineer, and the study’s first author, states, “We are the first to establish a connection between the potential influence of fat-resident senescent cells on brain a-klotho. This could provide another path to explore the effects of peripheral senescent cells on brain aging.” The protein a-klotho plays a crucial role in maintaining overall health. Its levels tend to decline as people age and are particularly reduced in various diseases such as Alzheimer’s, diabetes, and kidney disease.
Research on animals has revealed that reducing a-klotho in mice results in a shorter lifespan, while increasing a-klotho levels by inserting a gene that triggers its production can extend their lifespan by 30%. Increasing a-klotho levels in humans has been a significant objective in research; however, achieving this has been challenging due to its large size and instability. Direct introduction poses issues, as it necessitates intravenous administration rather than oral consumption. The current research demonstrates that senolytics, which can be taken orally, boost a-klotho levels in individuals suffering from idiopathic pulmonary fibrosis, a condition linked to senescence that results in frailty, severe breathing problems, and death.
This study received support from various organizations, including the National Institute of Health, the Translational Geroscience Network, Robert and Arlene Kogod, the Connor Group, Robert J. and Theresa W. Ryan, and the Noaber Foundation. Where can you get senolytic drugs? The senolytic drug dasatinib isn’t available as an over-the-counter drug. But quercetin is available in supplement form. You can also ramp up your quercetin intake by eating more onions, apples (with the skin!), citrus fruits, and parsley. It can’t hurt, and these delicious foods are easy to find at your grocery store or local farmer’s market. Read more: Owen Gregorian
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