A Drug Combination That Selectively Kills Senescent Cells Could Advance Anti-aging Research

Aging is a natural process, all people will gradually age with age, it seems to be an irreversible natural law. However, in recent years, with the acceleration of global aging, countries around the world have set off an upsurge in anti-aging research, and various anti-aging drugs and therapies have been discovered one after another, such as niacinamide, metformin and senolytics therapy.

Dr. James Kirkland from the Mayo Medical Center in the United States published a paper in the journal Aging Cell, reporting a class of drug combinations that selectively kill senescent cells-Senolytics. Senolytics therapy consisting of dasatinib and quercetin selectively induces senescent cell death. Among them, dasatinib can clear senescent human adipocyte progenitor cells, while quercetin can kill senescent human endothelial cells and mouse bone marrow stem cells, and the combined effect of the two is stronger.

Alpha-Klotho is an anti-aging protein in the body that reduces the harmful changes that come with aging and disease. Decreasing α-Klotho is associated with many age-related diseases while increasing α-Klotho has therapeutic potential. However, there is currently no strategy to increase α-Klotho that is easy to translate into clinical applications.

This study shows that an orally available, clinically translatable drug combination that selectively kills senescent cells, Senolytics, can selectively eliminate senescent cells in naturally aging mice, diet-induced obese mice, and mice with senescent cell transplantation. , increasing α-Klotho levels. In addition, increased levels of α-Klotho in the urine were also observed in patients with idiopathic pulmonary fibrosis (IPF) treated with Senolytics.

This study shows that Senolytics can restore the expression level of the anti-aging protein α-Klotho by targeting senescent cells. It opens up new avenues for anti-aging research and clinical applications. Senescent cells are a key driver of aging in the body, and eliminating senescent cells can delay or alleviate many age-related diseases.

In the new study, the team validated the effects of Senolytics in naturally aging mice, mice with diet-induced obesity, and mice transplanted with senescent cells, showing that in all three mice with increased senescent cell load, oral administration of Senolytics resulted in specific clearance of senescent cells and increased α-Klotho levels in the lobes, kidneys, and brain of mice.

The research team further validated it in patients with idiopathic pulmonary fibrosis (IPF) treated with Senolytics and found that α-Klotho levels in their urine were also increased.