Study Uncovers a Way to Identify Senescent Cells

Senescent cells, sometimes called zombie cells, pose a challenge for both aging research and disease treatment. These non-dividing cells linger in tissues instead of dying, emerging in cancer, Alzheimer’s disease, and aging-related processes. Removing or repairing these cells has potential therapeutic promise, but identifying them within healthy tissue remains difficult. Researchers at Mayo Clinic have reported an experimental approach that uses aptamers to tag these elusive cells, a step that could eventually aid in targeting or studying senescent cells in humans.

The study, published in Aging Cell, involved the screening of more than 100 trillion random DNA sequences to discover rare aptamers that attached selectively to senescent cell surface proteins in mouse cells. “This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones,” explains senior author Jim Maher, III. "Though this study is a first step, the results suggest the approach could eventually apply to human cells."

The project, which began organically through a conversation between two graduate students, has provided new information about senescent cells beyond a way to tag them. "To date, there aren't universal markers that characterize senescent cells," says Dr. Maher. "Our study was set up to be open-ended about the target surface molecules on senescent cells. The beauty of this approach is that we let the aptamers choose the molecules to bind to."

The study found several aptamers latched onto a variant of a specific molecule on the surface of mouse cells, a protein called fibronectin. The role of this variant fibronectin in senescence is not yet understood. The finding means that aptamers may be a tool to further define unique characteristics of senescent cells.

Additional studies will be necessary to find aptamers that can identify senescent cells in humans. Aptamers with the ability to latch onto senescent cells could potentially deliver a therapy directly to those cells.

"This project demonstrated a novel concept," says Dr. Maher. "Future studies may extend the approach to applications related to senescent cells in human disease."