Study finds that common supplement fights aging and age-related disease in mice

New research from the University of Chicago shows that vanadyl sulfate, a mineral dietary supplement, extended the lifespan of mice and helped limit the effects of aging and several age-related chronic diseases, including diabetes, heart disease, and liver disease.

The supplement appears to work by triggering processes that kill senescent cells, aging cells that stop dividing but remain active. These so-called “zombie cells” can accumulate in the body and cause inflammation and tissue dysfunction. They have been linked to several diseases including cancer, diabetes, heart disease, liver disease, and pulmonary fibrosis.

“Aging is partly a process of accumulating senescent cells. If those cells cannot be cleared or accumulate beyond the capacity to remove them, then they can lead to inflammation and just make the aging worse,” said Jing Chen, PhD, Janet Davison Rowley Distinguished Service Professor of Medicine and a senior author of the new study, published in Nature Aging.

Targeting effects on aging and disease

Chen’s lab studies how chemicals circulating in the blood, such as nutrients from diet and metabolites produced by the microbiome, influence health. His group has developed a library of hundreds of molecules that they can test for effects on different cell types. Recently, they identified two different dietary nutrients (Fan, et al., Nature 2023; and Zhang, et al., Cell Reports Medicine 2025) that improve the ability of immune cells to fight cancer.

This time, they wanted to see which nutrients could influence aging by eliminating excess senescent cells. Testing against senescent cells in the lab identified vanadyl sulfate, a trace mineral that is found naturally in shellfish, mushrooms, and soybeans, as a top candidate. It is also sold over the counter as a dietary supplement; athletes often take it to help muscle growth because it is believed to mimic the function of insulin and help cells process glucose.

Jiacheng Li, PhD, a postdoctoral scholar in Chen’s lab, led the project, along with former UChicago postdoc Rong Wu, PhD. They partnered with the lab of Chuan He, PhD, John T. Wilson Distinguished Service Professor of Chemistry and Professor of Biochemistry and Molecular Biology, to understand exactly how vanadyl sulfate was able to selectively kill senescent cells without affecting healthy cells.

Li and Wu worked closely with Fan Yang, PhD, a postdoc in He’s lab, to carry out a series of molecular and genetic analyses. They saw that vanadyl sulfate affected protein folding processes inside senescent cells by interfering with the formation of certain chemical bonds. When proteins do not fold properly, they aggregate into clumps inside cells, which eventually build up to the point that the cells can’t process them and die. Senescent cells are already prone to this issue due to a weakened reductive ability to maintain the chemical balance needed for proper protein folding. As a mild oxidant, vanadyl sulfate exacerbated this problem in senescent cells, but younger, healthy cells have the sufficient reductive ability to withstand the effects of vanadyl sulfate.

Aging mice (76 weeks old) were given vanadyl sulfate in their drinking water over four weeks, and it improved common signs of aging. Those given the supplement had improved physical endurance and muscle strength, reduced fat accumulation, better insulin sensitivity, and improved liver and kidney function compared to controls. Their lifespan was also extended by seven percent.

The researchers also worked with Janane Rahbani, PhD, Assistant Professor of Medicine and a member of the Cancer Metabolomics Research Center led by Chen, to exclude potential “off target” effects of vanadyl sulfate on metabolism in mice. Rahbani has implemented a powerful metabolic caging system for mice that houses them in specialized enclosures that automatically monitor activity, food and water intake, weight, body mass, and oxygen consumption.

When tested in several mouse models of age-related diseases, including diabetes, liver fibrosis, atherosclerosis, and lung fibrosis, the supplement improved symptoms for all those conditions as well.

Clearing the way for improved health

Chen and his team are now working with chemists to design new formulations of vanadyl sulfate to improve its potency and delivery in cells, with the hopes of testing them in more animal disease models, and possibly some day in human clinical trials as supplements to complement disease therapies.

“We assume the way to prevent aging is to slow down healthy cells to prevent them from deteriorating, but what we see here is that if you remove the senescent cells, you provide space and capacity for new cells to replace them and improve overall health,” he said. “This is not just about aging. One day this could be part of prevention for these age-related chronic diseases as well.”