Groundbreaking new drug promises to extend human life by 30%

[Apr. 4, 2023: Robert Nellis, Mayo Clinic]

Scientists may never find the elixir of life, but they are finding new ways to extend our life spans. One day, protecting our cells from aging may be as easy as taking a pill. Mayo Clinic researchers say senolytic drugs can boost a key protein in the body that may protect older people against aspects of aging and a range of diseases. Their findings, which are published in eBioMedicine demonstrate this in mice and human studies.

Senolytics developed at Mayo Clinic and given once clear the bloodstream of senescent or "zombie" cells. These cells contribute to multiple diseases and negative aspects of aging. This study shows that the removal of senescent cells significantly boosts the production of a protective protein called a-klotho.

Zombie cells (which are called senescent cells in the scientific community) are cells in your body that “refuse to die.”

A cell typically begins as a normal one, doing its job to support the body. Then, it might suffer from some sort of stress — be it oxidative stress, a viral infection, or another factor. That stress triggers the cell to do one of three things: repair itself, die, or become a zombie cell.

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Now, zombie cells aren’t all bad. Research from 2017 shows that cellular senescence (the transformation of regular cells into zombie cells) is a beneficial response to tumor growth. Instead of multiplying out of control and helping form a tumor, a cell will become a zombie and cease growth.

However, zombie cells in other contexts have negative effects. As you age, these zombies build up in the body. They can make it difficult for your body to repair tissue, and they can release chemicals that harm normal cells nearby. In fact, research links zombie cells to several age-related diseases, including atherosclerosis (a form of heart disease), diabetes, and lung disease.

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.

They also demonstrated that using the senolyitics desatinib plus quercitin in three types of mice that a-klotho was increased. And then after administering desatinib plus quercitin in clinical trial participants with idiopathic pulmonary fibrosis, that a-klotho also increased.

"We also are first to link the potential impact of fat-resident senescent cells on brain a-klotho," says Yi Zhu, Ph.D., a Mayo Clinic physiologist and biomedical engineer, and first author of the study. "This may open another avenue to investigate the impact of peripheral senescent cells on brain aging."

The protein a-klotho is important to maintaining good health, as it tends to decrease with age, and especially decreases in multiple diseases, including Alzheimer's, diabetes and kidney disease.

Animal studies have shown that decreasing a-klotho in mice shortens life span and increasing a-klotho in mice by inserting a gene that causes its production increases life span by 30%.

Discovering ways to increase a-klotho in humans has been a major research goal, but that has been difficult because of its size and instability. Introducing it directly is problematic, as it would have to be administered into a vein instead of by mouth.

This study shows that senolytics, which can be administered orally, increase a-klotho in humans with idiopathic pulmonary fibrosis, a senescence-associated disease that leads to frailty, serious breathing difficulties and death.

The study was supported by 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.

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.

Note: Materials provided above by Mayo Clinic. Content may be edited for style and length.

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