Senescent Cells and Aging: What Senolytic and Exercise Studies Show

By Dr. Ryan Kneessi, ND · Move Forward Natural Health, Odenton, MD · Last reviewed: October 26, 2026

When researchers talk about why our bodies change with age, they often use a framework called the hallmarks of aging. It groups the biology of aging into a dozen interconnected processes, such as changes in how genes are switched on, wear and tear on mitochondria, and a decline in the body’s cellular recycling systems. One of the hallmarks that has drawn the most attention over the past decade is cellular senescence, sometimes described in the popular press as “zombie cells.” In this article, I want to explain what senescent cells are, walk through a few of the most important studies, and share how I think about this research as a functional medicine doctor.

What is a senescent cell?

Every day, some of the cells in your body are damaged by things like DNA errors, oxidative stress, or simply having divided many times. A damaged cell has a few options. It can repair itself, it can quietly self-destruct, or it can enter a state called senescence, in which it permanently stops dividing but stays alive. In the short term, this is useful. Senescence keeps damaged cells from multiplying, and senescent cells play helpful roles in wound healing and development.

The trouble seems to come when senescent cells accumulate faster than the immune system can clear them, which tends to happen as we get older. Senescent cells release a blend of inflammatory proteins, enzymes, and growth signals that scientists call the senescence-associated secretory phenotype, or SASP. Over time, this steady release may contribute to the low-grade, body-wide inflammation that researchers call inflammaging, and it can nudge neighboring healthy cells toward senescence as well. Researchers often track senescence with markers such as the proteins p16 and p21, which act as brakes on cell division.

The mouse study that changed the conversation

A 2018 study from the Mayo Clinic, led by Ming Xu and James Kirkland and published in Nature Medicine, asked a direct question: can senescent cells by themselves cause problems, and does removing them help? The researchers transplanted a relatively small number of senescent cells into young mice and found that this was enough to cause lasting declines in physical function, such as walking speed, grip strength, and endurance. The transplanted cells also seemed to spread senescence to the host’s own tissues. Older mice were even more sensitive, needing fewer transplanted cells to show the same effects, and they also had shorter survival.

The team then tested a combination of two compounds, the prescription drug dasatinib and the plant flavonoid quercetin, given intermittently. This combination belongs to a class called senolytics, which are designed to selectively clear senescent cells. In both the transplanted young mice and naturally aged mice, the combination eased physical dysfunction. In mice that started the combination at an age the authors compare to roughly 75 to 90 human years, median remaining lifespan was 36 percent longer than in a comparison group that received an inactive solution. The authors described this as proof-of-concept evidence, which is the right way to read it, since mouse results do not always carry over to people. You can read the free full text on PubMed Central.

What the first small human studies found

Because senescent cells are linked to many age-related conditions, the first human trials of senolytics were done in people who already had serious health problems. In a 2019 open-label pilot study published in EBioMedicine, Jamie Justice and colleagues gave the same dasatinib and quercetin combination three days a week for three weeks to 14 people with idiopathic pulmonary fibrosis, a progressive lung disease that has been strongly tied to senescence. The main goal was to see whether such a study was feasible, and every participant stayed in the study. Physical function measures, including six-minute walk distance, gait speed, and the time needed to rise from a chair, improved significantly, while lung function itself did not change. Side effects were mostly mild to moderate, and one serious adverse event was reported. The full text is free on PubMed Central.

Later that year, LaTonya Hickson and colleagues reported a second small study in EBioMedicine, this time in nine adults with diabetic kidney disease who took the combination for just three days. When the researchers compared tissue samples taken before and 11 days after dosing, they found fewer senescent cells in fat tissue and skin, along with lower blood levels of several SASP proteins, including IL-6. This was the first peer-reviewed report showing directly that a senolytic approach could lower senescent cell burden in humans. You can read it on PubMed Central.

It is important to keep these human studies in perspective. They were very small, they had no placebo group, and they involved people with specific medical conditions. Dasatinib is a prescription cancer medication with real risks, and the doses of quercetin used were far higher than what people get from food. These studies are not a reason to try a senolytic protocol on your own, and larger, placebo-controlled trials are still underway.

Exercise and markers of senescence

The study I find most practical comes from the same Mayo Clinic research group. In 2021, Davis Englund, Nathan LeBrasseur, and colleagues published a study in Aging Cell in which older adults completed a 12-week structured exercise program that combined progressive strength and endurance training two days a week. By the end of the program, participants had lost body fat and improved their grip strength, their repeated sit-to-stand time, and their score on a standard balance and mobility test called the timed up and go. They also reported less fatigue and better quality of life.

The most interesting part was what happened inside their immune cells. In circulating T cells, the expression of p16, p21, and several inflammation-related genes went down after the program, and the blood levels of multiple senescence-related proteins fell as well. The authors described this as the first evidence in humans that a structured exercise program can lower biomarkers of senescent cell burden. Like the other studies, it was modest in size and did not include a control group, so it is a starting point rather than the final word. The free full text is on PubMed Central.

How I think about senescence in a functional medicine plan

Senescence research is still young, and there is no routine lab test I can order that measures how many senescent cells someone has. What I can do is look at the broader picture that this research points to. Chronic inflammation, blood sugar regulation, muscle strength, and fitness are all connected to the aging processes described in the hallmarks framework, and many of them can be measured and followed over time. I often start with markers such as the hs-CRP test for inflammation, and I pay close attention to measures of physical capacity, which I explain in my articles on VO2 max and longevity and strength training for longevity.

Senescence also overlaps with other hallmarks of aging. If you would like to read more, my articles on autophagy, mitochondrial health, and epigenetic clocks and the pace of aging look at closely related parts of the same story. The common thread is that the habits with the strongest evidence, such as regular strength and endurance training, good sleep, and a whole-food diet, appear to touch many of these processes at once. Before starting a new exercise program, especially if you have a heart, lung, or joint condition, it is a good idea to check with your clinician about what level of activity is right for you.

Frequently asked questions

Sources

• Xu et al. Senolytics Improve Physical Function and Increase Lifespan in Old Age. Nature Medicine. 2018. Free full text on PubMed Central.
• Justice et al. Senolytics in Idiopathic Pulmonary Fibrosis: Results from a First-in-Human, Open-Label, Pilot Study. EBioMedicine. 2019. Free full text on PubMed Central.
• Hickson et al. Senolytics Decrease Senescent Cells in Humans: Preliminary Report from a Clinical Trial of Dasatinib plus Quercetin in Individuals with Diabetic Kidney Disease. EBioMedicine. 2019. Free full text on PubMed Central.
• Englund et al. Exercise Reduces Circulating Biomarkers of Cellular Senescence in Humans. Aging Cell. 2021. Free full text on PubMed Central.

This article is for educational purposes only and is not medical advice. It does not replace an individual evaluation. Talk with your healthcare provider before making changes to your diet, exercise, supplements, or medications, especially if you are pregnant, nursing, or managing a health condition.