Scientists have long suspected that a class of aging cells, the senescent cells that refuse to die and keep sending out inflammatory signals, quietly drive many of the diseases that come with growing old. In a set of seven studies from Mayo Clinic's Kogod Center on Aging, researchers have begun to see these cells not as a single uniform problem but as a varied population whose character depends on where they sit and what set them off. Their work suggests that the inflammation they fuel might be interrupted at its source, leaving the cells themselves in place, a possibility that offers a quiete
Mayo Clinic Studies Map Why 'Zombie' Aging Cells Differ and How Their Harmful Inflammation Might Be Curbed
Moving beyond the idea that every harmful aging cell must be destroyed
Mark
So what's actually new here? Scientists already knew zombie cells were bad.
Mimi
The shift is from 'senescent cells matter' to 'which ones matter and why.' These studies show the cells differ by tissue and by what made them senescent.
Mark
And that matters for treatment how?
Mimi
If you can't tell the cells apart, you can't target the harmful ones. The SenMayo gene set is meant to fix that, and it was tested on bone biopsies from older adults.
Luke
Worth noting that's identification, not treatment. The source says SenMayo is widely used, but that's different from showing it guides therapy.
Mark
The mitochondria piece sounded important.
Mimi
Yes. Mitochondrial DNA and RNA can trigger immune responses, and metabolic changes can alter inflammatory genes epigenetically. That suggests blocking the inflammation without killing the cells.
Luke
Suggests is the key word. The source says researchers may eventually be able to do that. Nothing here shows it working.
Mark
What about the tomato compound?
Mimi
It was one of several approaches tested in older mice, along with senolytic drugs and genetic techniques. Results included less inflammation, less frailty, and better cognitive task performance.
Luke
Those gains varied by approach, and the source doesn't give sizes or say which approach did what. It's mice, and safety in people is untested.
Mark
And the blood marker?
Mimi
IL-23R might help track aging changes and show whether a treatment works. It's a potential biomarker, not a validated test.
Il Polso
- Senescent 'zombie' cells refuse to die and keep broadcasting inflammation, and researchers now find that they come in many different forms.
- Mitochondrial DNA and RNA leaking into the cell's interior set off immune alarms that keep the inflammation running.
- Scientists are testing whether the inflammatory circuitry can be switched off while the cells themselves are left intact, sidestepping the need to destroy them all.
- In aging mice, treatments reduced inflammation and eased frailty, brain inflammation, and cognitive decline, but none of it has been proven safe or effective in humans.
Scientists have long suspected that a class of aging cells, the senescent cells that refuse to die and keep sending out inflammatory signals, quietly drive many of the diseases that come with growing old. In a set of seven studies from Mayo Clinic's Kogod Center on Aging, researchers have begun to see these cells not as a single uniform problem but as a varied population whose character depends on where they sit and what set them off. Their work suggests that the inflammation they fuel might be interrupted at its source, leaving the cells themselves in place, a possibility that offers a quieter kind of hope than wholesale destruction. Yet the promise remains rooted in mice, and whether these insights will reach people is a question the field has not yet answered.
Seven new studies from Mayo Clinic's Robert and Arlene Kogod Center on Aging, published in Nature journals, return to a stubborn question in aging research: which of the so-called zombie cells are truly causing harm, and what can be done about them. Senescent cells are aging cells that persist in the body rather than dying off, and they feed inflammation and disease. This work moves past confirming their importance and asks how to tell different types apart, why they keep producing damaging inflammation, and how that damage might be reduced.
The first finding is that these cells vary far more than scientists assumed, shaped by their tissue location and by what pushed them into senescence. To help identify them more reliably, the team developed the SenMayo gene set, which recognizes senescent cells by their gene activity patterns across tissues and experimental systems. It has since become a widely used resource. Other studies traced the persistent inflammation to malfunctioning mitochondria, the cell's energy structures. Mitochondrial DNA and RNA can trigger immune responses, and shifts in mitochondrial metabolism can alter inflammatory gene activity through epigenetic changes that affect how genes are switched on without altering the DNA itself.
These findings suggest a different therapeutic path: if the pathways sustaining inflammation can be interrupted, the damaging signals might be quieted while the senescent cells remain, rather than attempting to eliminate every one.
In older mice, the team tested senolytic drugs that destroy senescent cells, a natural compound found in tomatoes, and genetic techniques aimed at particular aging cell populations. Depending on the approach, inflammation fell, and frailty, brain inflammation, and cognitive performance improved. Researchers also identified IL-23R as a possible blood and tissue marker of senescence-linked aging, which could one day show whether a treatment is working, and mapped senescent microglia in the aging mouse brain.
The studies feed into SenNet, a nationwide National Institutes of Health project mapping where senescent cells appear in human tissues over a lifetime, and into Mayo Clinic's Precure Research initiative, which aims to intervene before harmful biological changes become disease. The researchers are clear that these results remain preliminary. The animal findings have not been tested in people, and whether any approach is safe and effective for humans will require much more research. The next markers to watch are the SenNet maps and the continued study of IL-23R in the blood.
Seven new studies from Mayo Clinic's Robert and Arlene Kogod Center on Aging, published in Nature journals, take on a question that has dogged aging research for years: which of the so-called zombie cells are actually doing the damage, and what can be done about them. Senescent cells are aging cells that stay in the body instead of dying off, and they contribute to inflammation and disease. The new work goes past confirming that they matter and asks how to recognize different types, why they generate harmful inflammation, and how their effects might be reduced.
The first finding is that these cells are far more varied than scientists had assumed. Their characteristics shift depending on where in the body they sit and on what pushed them into senescence. Reliable identification has long been a major obstacle in the field, and the team's answer was a tool called the SenMayo gene set, which uses patterns of gene activity to spot senescent cells more consistently across tissues and experimental systems. The researchers tested it on bone biopsies from older adults. They also found that the gene signature faded after senescent cells were removed in preclinical experiments. SenMayo has since become a widely used resource for people studying aging and related diseases. Endocrinologist Sundeep Khosla, M.D., was senior author of that paper, which carries the title "A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues." Nathan LeBrasseur, Ph.D., Diana Jurk, Ph.D., João Passos, Ph.D., and LaTonya Hickson, M.D., also contributed. Darren Baker, Ph.D., was senior author of a further paper, "Senotypes define the diverse landscape of senescent cells."
Other studies looked at why senescent cells keep producing inflammatory signals. Several of the mechanisms involve malfunctioning mitochondria, the structures that supply much of a cell's energy. In one pathway, DNA and RNA originating from mitochondria set off immune responses that feed inflammation. In another, changes in mitochondrial metabolism influence inflammatory gene activity through epigenetic mechanisms, which alter how genes are switched on or off without changing the DNA sequence itself. Dr. Passos was senior author of three papers on these mechanisms and on the diversity of senescent cells, including "Distinct senotypes in p16- and p21-positive cells across human and mouse aging tissues," "Mitochondrial metabolism and epigenetic crosstalk drive SASP," and "Mitochondrial RNA cytosolic leakage drives the SASP."
Those results point toward a different kind of treatment. If the pathways that sustain chronic inflammation can be interrupted, it may be possible to quiet the damaging signals while leaving the senescent cells themselves in place, rather than trying to destroy every one of them.
The team also tested ways to reduce senescent cells or limit the harm they cause: senolytic medications designed to eliminate them, a natural compound found in tomatoes, and genetic techniques aimed at particular populations of aging cells. In older mice, depending on the approach, researchers saw lower inflammatory measures and improvements in physical frailty, inflammation in the brain, and performance on cognitive tasks.
Marissa Schafer, Ph.D., whose laboratory directed several of the investigations, was lead author of two studies on biomarkers and interventions. One identifies IL-23R as a senescence-linked marker of aging that can be found in the blood and in tissue, a possible way to gauge aging-related changes and eventually to tell whether a treatment is working. The other, on spatial mapping and senolytic targeting of senescent and disease-associated microglia in the white matter of aged mouse brains, examines the brain. "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," she said, calling that the necessary groundwork for therapies that support healthy aging.
The studies also feed into the Cellular Senescence Network (SenNet) Consortium, a nationwide project funded by the National Institutes of Health Common Fund. It brings together researchers across the United States to map where senescent cells occur in different human tissues and how they change over a lifetime. The work likewise supports Mayo Clinic's Precure Research initiative, which aims to help physicians identify and intervene in harmful biological changes before they become disease.
The medical findings remain preliminary. The animal results have not been tested in people, and whether any of these approaches is safe and effective in humans will take further research. The next things to watch are the SenNet mapping and the continuing work on IL-23R as a blood marker.
Citazioni salienti
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.— Marissa Schafer, Ph.D., Mayo Clinic
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