New tools to identify senescent cells, a candidate blood biomarker and preclinical tests of targeted treatments aim to move aging research from broad strokes to precision.
As we age, some of our cells stop dividing but refuse to die. These senescent cells, nicknamed “zombie” cells, linger in tissues and pump out inflammatory molecules that can damage their neighbours. Over decades, their accumulation is thought to contribute to frailty, chronic inflammation and many of the diseases of old age.
Researchers at Mayo Clinic’s Robert and Arlene Kogod Center on Aging have now published seven studies across Nature journals that aim to make the study of these cells far more precise. The work offers new tools for identifying senescent cells, sheds light on what drives their inflammatory output and tests ways to target them in preclinical models.
“This body of work is moving the aging field forward to precisely identify, understand and target the specific senescent cells that contribute to age-related dysfunction, which is the necessary groundwork to develop new therapies that support healthy aging,” said Marissa Schafer, Ph.D., whose laboratory led several of the studies.
From a lab curiosity to a drug target
Cellular senescence was first described in the early 1960s, when biologist Leonard Hayflick showed that normal human cells grown in a dish stop dividing after a limited number of divisions. For years it was regarded as a laboratory curiosity. That changed as researchers found senescent cells accumulating in aging tissues and showed that clearing them in mice could delay age-related problems.
Mayo Clinic has been central to that story. In 2015, Mayo researchers reported the first senolytics, drugs that selectively kill senescent cells, and the field has since grown into one of the most active areas of aging research.
Senescence is not simply a malfunction. It likely evolved partly as a defence against cancer, since a damaged cell that permanently stops dividing cannot become a tumor, and senescent cells help orchestrate wound healing. In young bodies, the immune system clears them efficiently. As people age, that clearance appears to slow, and senescent cells accumulate in many tissues. Small early human studies of senolytic drugs have been run in conditions such as lung fibrosis, but large trials showing clear benefits are still lacking.
But senescent cells turned out to be more varied than first thought. They differ by tissue, by what triggered them and by which molecular markers they carry. Two of the most widely used markers, the proteins p16 and p21, label overlapping but distinct populations.
Finding the right cells
Several of the new studies tackle the problem of identification. One introduces SenMayo, a gene set designed to identify senescent cells across tissues. According to the release, it was validated in aged human bone biopsies and its signal decreased after senescent cells were cleared in preclinical models. Sundeep Khosla, M.D., is senior author of that paper.
Other papers map the diversity of senescent cells, describing distinct “senotypes” in p16- and p21-positive cells across human and mouse tissues. Darren Baker, Ph.D., is senior author of one such study, and João Passos, Ph.D., of another.
A further study, led by Schafer, mapped senescent and disease-associated microglia, the brain’s resident immune cells, in the white matter of aged mouse brains and tested senolytic targeting of those cells.
A possible blood test for biological age
One study identified IL-23R, a receptor involved in immune signaling, as a possible biomarker of aging that can be measured in blood and tissue. A reliable blood marker of senescent cell burden would be valuable both for estimating a person’s biological age and for tracking whether future treatments are working. The release gives no validation figures, so how well IL-23R performs remains to be seen.
Switching off the damage
Other papers explore why senescent cells become so inflammatory. The collection of molecules they secrete is known as the senescence-associated secretory phenotype, or SASP. The studies show that dysfunctional mitochondria, the cell’s energy producers, promote this inflammation through several routes. In one, mitochondrial DNA and RNA leak into the cell and set off immune alarms. In another, mitochondrial metabolism controls epigenetic switches that turn inflammatory genes on.
Those mechanisms point to a different therapeutic strategy. Rather than killing senescent cells outright, it may be possible to shut down the harmful inflammation they produce while leaving the cells in place.
Tests in aged mice
The team also tested treatments. Studies examined senolytic drugs, a compound found in tomatoes and genetic approaches that target senescent cells. In aged mice, these reduced inflammation and improved measures of frailty, brain inflammation and cognitive performance.
The release is careful to note that these are preclinical results requiring further work before any clinical use, and it reports no doses, sample sizes or effect sizes. Treatments that help old mice frequently fail to translate to people, and the long-term safety of removing or reprogramming senescent cells in humans is still being studied.
Toward precision aging medicine
The work is part of the SenNet Consortium, a program launched by the National Institutes of Health Common Fund to build detailed atlases of senescent cells across human tissues and the lifespan. It is also tied to Mayo Clinic’s Precure Research initiative, which aims to help clinicians predict and intercept disease processes before illness develops.
The release argues that the field is moving from establishing that senescent cells contribute to aging toward identifying which ones matter most and how best to target them. That shift, from indiscriminate elimination to precision, is likely to define the next phase of aging research.
Full author lists, disclosures and funding details are in the individual papers.
Notes
- Martini, H., et al. “Mitochondrial metabolism and epigenetic crosstalk drive SASP.” Nature, 29 July 2026. https://www.nature.com/articles/s41586-026-10791-2.
- Other studies in the collection include “A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues”; “Distinct senotypes in p16- and p21-positive cells across human and mouse aging tissues”; “Mitochondrial RNA cytosolic leakage drives the SASP”; “IL-23R is a senescence-linked circulating and tissue biomarker of aging”; “Spatial mapping and senolytic targeting of senescent and disease-associated microglia in aged mouse brain white matter”; and “Senotypes define the diverse landscape of senescent cells.”
- Mayo Clinic. “Mayo Clinic research advances understanding of senescent ‘zombie’ cells, healthy aging.” EurekAlert!, 29 July 2026. https://www.eurekalert.org/news-releases/1138104.
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