New DNA Aptamers Reveal 'Zombie' Senescent Cells — Breakthrough for Aging Research and Therapies

DNA aptamers uncover senescent “zombie” cells that drive age-related disease

Aging often appears invisibly at the cellular level: some cells stop dividing yet remain metabolically active and harmful. These so-called “zombie” or senescent cells secrete inflammatory and tissue-damaging molecules that, over time, contribute to conditions such as arthritis, fibrosis and Alzheimer’s disease. A team at the Mayo Clinic reports a promising DNA-based method to detect these cells in mice, a step that could transform how researchers map, diagnose, and eventually treat age-related tissue damage.

How the discovery was made

Led by Keenan S. Pearson and L. James Maher III, the researchers used SELEX (Systematic Evolution of Ligands by EXponential enrichment) to screen an enormous library—more than 100 trillion random DNA sequences—for short synthetic strands (aptamers) that preferentially bind senescent cells. Instead of starting from a known marker, the open-ended SELEX approach let the cells "choose" which DNA sequences adhered to them.

Working with cultured mouse fibroblasts, the team induced senescence with DNA-damaging drugs and compared binding to healthy cells. After multiple selection cycles they isolated two aptamers, 6756 and 6762, that consistently distinguished senescent from non-senescent mouse cells. The aptamers also marked senescent cells in other mouse cell types (liver, muscle) and detected senescence caused by radiation or chemical stress.

What the aptamers bind — and why it matters

Protein analysis revealed both aptamers bind a variant of fibronectin called FN-EDA1, an extracellular matrix isoform enriched in aging or injured tissues. Fibronectin helps tissues repair after injury, but certain variants can indicate scarring and stiffness. By recognizing FN-EDA1, the aptamers report not only the presence of senescent cells but also tissue-level changes associated with biological aging.

In one striking experiment, aptamer 6762 produced almost no fluorescent signal in young mouse lungs but bright clustered staining in older lungs. In genetically engineered mice that clear senescent cells after drug treatment, the fluorescent signal nearly disappeared—supporting the aptamer’s specificity for the biological signature of senescence rather than nonspecific binding.

Limitations and next steps

Importantly, these exact aptamers did not bind the same targets on human cells, so they must be re-engineered and validated for human use. Further work is needed to confirm sensitivity and specificity across tissues, to test safety and delivery methods for therapeutic use, and to determine whether FN-EDA1 marks all types of senescence or a subset associated with matrix remodeling.

Clinical potential

Aptamers are generally cheaper and easier to produce than antibodies and can be engineered to carry drugs or imaging agents. If adapted for humans, aptamer-based diagnostics could help measure "cellular age" in tissues, and targeted therapies might clear or modulate senescent cells while sparing healthy cells—potentially delaying or reducing diseases driven by chronic inflammation and tissue breakdown.

“It’s an exciting new way to define what it means for a cell to be senescent,” said Dr. L. James Maher III. Keenan Pearson added that aptamers’ adaptability could enable future human applications.

The full study is available online in the journal Aging Cell. While promising, translation to human diagnostics and therapies will require re-engineering of aptamers for human targets and extensive validation.