They’re commonly known as “zombie cells,” but senescent cells are no work of fiction. Discovered in the early 1960s by Leonard Hayflick and Paul Moorhead, senescent cells are cells that remain metabolically active despite being damaged or stressed to the point that they permanently stop dividing. Unlike healthy cells, senescent cells no longer function normally and cannot continue the process of replication. Instead, they linger in tissues throughout the body, secreting a mix of inflammatory molecules known as the senescence-associated secretory phenotype (SASP).

Initially, cellular senescence serves an important protective role, helping prevent damaged cells from becoming cancerous and supporting processes such as wound healing. However, the accumulation of senescent cells over time can become harmful, especially as natural clearance mechanisms, including immune system activity, decline with age. Senescent cells and SASP contribute to tissue damage, promote senescence in neighboring cells, and are increasingly associated with chronic inflammation and age-related diseases.

But researchers are exploring whether senolytics may offer a way to address this process.

Clearing Out the Zombies

Finding a solution to cellular senescence and its effects on aging has led researchers to senotherapeutics — a group of therapies designed to target senescent cells and their harmful effects. Senotherapeutics include senomorphics, which aim to reduce the secretion of pro-inflammatory substances associated with SASP, and senolytics, which work by selectively targeting senescent cells and triggering apoptosis while sparing healthy cells.

“Senotherapeutics is a new concept in antiaging dermatology,” explains Zoe Diana Draelos, MD, a consulting professor of dermatology at Duke University School of Medicine in Durham, North Carolina. “The new concept of cellular senescence in dermatology has led to the search for senotherapeutics, which are small molecules designed to target senescent cells. Senotherapeutics can be divided into senolytics or senomorphics. Senolytics are designed to clear senescent cells through senolysis.”

Beyond dermatology, senolytics are gaining attention in longevity medicine because of their potential to remove senescent cells that contribute to chronic inflammation, impaired tissue function, and age-related decline.

“Intrinsic and extrinsic aging both contribute to cellular senescence,” Dr. Draelos points out, adding that intrinsic aging “is characterized by oxidative stress from bodily functions and telomere shortening,” while extrinsic aging is primarily driven by factors such as UV exposure and pollution.

To an extent, cellular senescence can be influenced through therapeutic and lifestyle approaches. Regular physical activity, for example, has been associated with improved cellular health and may help support the body’s natural clearance mechanisms. However, researchers are investigating whether senolytics may provide another strategy by targeting accumulated senescent cells before they contribute to broader tissue dysfunction.

Building on a Breakthrough

Researchers at the Mayo Clinic have been investigating how senescent cells contribute to aging and disease, and how senolytics may advance the goal of improving healthspan and maintaining function as we age.

In 2011, Mayo Clinic researchers found that removing senescent cells from mice delayed the onset of various age-related conditions, including cataracts and muscle weakness. The mice did not live longer, but they maintained better health throughout their lives — running longer, maintaining body weight, and showing fewer signs of age-related decline.

The discovery, considered a major breakthrough in aging research, helped accelerate interest in senotherapeutics and the development of senolytic therapies designed to target senescent cells. Because senolytics target specific survival pathways that are more active in senescent cells, researchers hope they may minimize effects on healthy tissues.

The research has continued at Mayo Clinic’s Robert and Arlene Kogod Center on Aging and around the world. Recent clinical studies are beginning to explore the safety, feasibility, and potential applications of senolytics in humans, including:

St. Jude Children’s Research Hospital

A first-in-survivor pilot study evaluating whether senolytic regimens can reduce markers of cellular senescence and improve frailty-related outcomes in adult survivors of childhood cancer.

Washington University School of Medicine

A Phase II clinical trial evaluating the safety, feasibility, and potential effects of senolytic therapy in older adults with amnestic mild cognitive impairment (MCI) or early-stage Alzheimer’s disease.

National Institutes of Health (NIH)

An NIH-supported frailty study evaluating dasatinib plus quercetin in people aging with HIV, examining effects on physical function and markers of cellular senescence.

Concluding Thoughts

Senolytic therapy is shaping up to be the next frontier in longevity medicine. While many questions remain about long-term safety, optimal treatment approaches, and their impact on human lifespan, early research has highlighted the potential of targeting senescent cells as a way to address some of the biological mechanisms associated with aging.

Sources:

Senolytics: from Pharmacological Inhibitors to Immunotherapies, a Promising Future for Patients’ Treatment

What Are Zombie Cells and How Do They Affect Your Health?

New Concepts in Antiaging Dermatology

Senolytics Under Scrutiny in the Quest to Slow Aging

Senolytics Hit the Clinic: Three 2025 Trials Define the Turn