Research & Discovery > What Are Zombie Cells?

What Are Zombie Cells?

By Alison Caldwell, Ph.D. Illustrations by Donna DeSmet

"Zombie cells" lurk within our bodies, accumulating as we age and contributing to a wide range of health problems. Also known as senescent cells, these cellular undead evade the body's normal clearance mechanisms and instead linger, secreting toxic substances that can damage surrounding healthy tissues.

At Mayo Clinic, researchers are at the leading edge in understanding how these zombie cells contribute to aging and disease, with promising developments that could help us age more gracefully.

Understanding the Cellular Undead

Throughout our lives, our cells experience wear and tear. When cells become damaged, they typically have two fates: repair themselves and continue functioning, or self-destruct through a process called apoptosis. Zombie cells, however, take a different path. They become senescent, meaning they neither repair properly nor die off.

First described in 1961 by biologists Leonard Hayflick and Paul Moorhead, a common cell (fibroblast) was found to divide only about 50 times before entering a twilight state. While they continue to perform their cellular duties to the best of their abilities, senescent cells secrete inflammatory molecules and other toxic substances — collectively known as the senescence-associated secretory phenotype (SASP) — that can compromise nearby healthy cells.

According to Nathan LeBrasseur, Ph.D., M.S., director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic, even if there are other healthy cells around, the toxic secretions of damaged zombie cells can poison healthy cells and negatively affect their function. Dr. LeBrasseur is also the Noaber Foundation Professor of Aging Research.

BECOMING A ZOMBIE CELL

CELL DAMAGE

When damaged by injury, disease or environmental cues, most cells either repair themselves or self-destruct via apoptosis. Zombie cells, however, become senescent, meaning they neither repair properly nor die off.

TOXIC SIGNALS

These senescent cells evade the body's normal clearance mechanisms. They linger in the tissue and secrete inflammatory molecules and other toxic substances — collectively known as the senescence-associated secretory phenotype (SASP) — that can compromise nearby healthy cells.

ACCUMULATION

In youth, the immune system is good at identifying and eliminating senescent cells. As we age, this clearing mechanism becomes less effective, allowing zombie cells to accumulate.

SENOTHERAPEUTICS

Removing zombie cells in mice delays the onset of a number of age-related disorders. As a result, scientists are working on developing senotherapeutics — drugs that can kill senescent cells or block their harmful secretions. The hope is that one day these therapies can be used to protect human health as we age.

How Do Zombie Cells Impact Our Health?

When we're young, the immune system is good at identifying and eliminating senescent cells. As we age, this clearing mechanism becomes less effective, allowing zombie cells to accumulate. This accumulation is associated with a long list of age-related conditions like tissue fibrosis, bone degeneration and chronic inflammation.

The presence of zombie cells can significantly affect healing processes. As Dr. LeBrasseur notes, these damaged cells can hinder normal tissue repair, creating an environment where even healthy cells struggle to function properly. This contributes to the progressive nature of aging, where health conditions begin to stack up. What might take 50 years to develop into a person’s first chronic disease might result in a second within just five years, and a third even more quickly.

Scientific Breakthrough of the Year

In 2011, Mayo Clinic researchers made a groundbreaking discovery that was recognized as one of the scientific breakthroughs of the year by the journal Science. By removing zombie cells in mice, they delayed the onset of various age-related disorders including cataracts and muscle weakness. The mice didn't live longer, but they maintained better health throughout their lives — running longer, maintaining weight and showing fewer signs of aging-related decline.

This discovery has led to the development of "senotherapeutics": drugs designed to target zombie cells. Varieties include senolytics, which kill senescent cells directly, and senomorphics, which suppress the harmful secretions of these cells. These approaches show promise in preclinical models, but more work is needed before they can be widely used in humans.

Better Health Through Graceful Aging

While pharmaceutical interventions are still being developed, there are proven ways to manage zombie cell accumulation. Dr. LeBrasseur, a self-described "exercise evangelist," emphasizes that regular physical activity both prevents senescent cell accumulation and promotes their clearance. He says that the usual recommendations for healthy aging — such as regular exercise, a healthy diet and socializing regularly with loved ones — are all critical for aging well.

The work at Mayo Clinic's Robert and Arlene Kogod Center on Aging continues to explore the effects of zombie cells, hoping to find ways to delay or prevent their negative impacts on our health. By taking a holistic, lifelong approach to managing senescent cells, we may be able to extend the individual “health span,” improving quality of life for aging adults everywhere.