Zinc Boosts Senescent Cells Clearance in Aged Mice
News related to:Albert Einstein College of Medicine · 3 min read
BRONX, N.Y., Oct. 5, 2026 /CourierPR/ -- Albert Einstein College of Medicine researchers have made a significant discovery that sheds light on why "zombie cells," also known as senescent cells, accumulate with age and contribute to chronic inflammation and age-related diseases. The study, published today in the journal Nature Aging, reveals that declining activity in a cellular recycling process called chaperone-mediated autophagy (CMA) plays a crucial role in the accumulation of these cells.
The research, led by Ana Maria Cuervo, M.D., Ph.D., distinguished professor of developmental and molecular biology and of medicine, and co-director of the Institute for Geroscience at Albert Einstein College of Medicine, helps explain why these cells, which have stopped dividing or functioning normally, linger in tissues and contribute to diseases such as lung fibrosis.
In experiments with mice, the researchers found that age-related changes in both senescent cells and the immune cells responsible for removing them allow these zombie cells to accumulate and play a role in disease. By restoring the cellular recycling process, the study suggests, the body's own defenses may be better equipped to clear these cells more effectively.
Dr. Cuervo, a leading authority on CMA, a process that enables the body's cells to remove and recycle damaged or unnecessary proteins, discovered that CMA activity declines with age. This decline contributes to the buildup of cellular "garbage" in neurons and other cells, which is linked to various age-related diseases such as Alzheimer's, vascular conditions, and diabetes.
In the new study, Dr. Cuervo and her team investigated whether declining CMA contributes to the accumulation of senescent cells that can disrupt healthy tissue function as we age. Most of the study's experiments were conducted in mice, while analyses of human lung tissue provided evidence that the findings may also be relevant to people.
The researchers found that when cellular recycling falters, zombie cells can accumulate and interfere with tissue repair. For instance, when the researchers used mice whose macrophages had been genetically altered to lack CMA, these mice accumulated more zombie cells at wound sites and their wounds healed more slowly. This indicates that CMA in macrophages is important for clearing senescent cells that can interfere with tissue repair.
The study also revealed that cells from old mice failed to increase their already low CMA activity when they became senescent, leading to the accumulation of undigested toxic substances that made nearby healthy cells more likely to turn into zombies and interfered with macrophages' ability to recognize and remove them. Additionally, the researchers found that CMA activity in older animals' macrophages was lower than that in younger animals, reducing their ability to engulf and eliminate senescent cells.
The research suggests that instead of trying to kill zombie cells, a new strategy could be to use a compound that both activates CMA to reduce the harmful effects of zombie-cell secretions and restores macrophages' ability to recognize and engulf zombie cells. The researchers had previously developed such a compound: a small-molecule CMA activator called CA77.1. Experiments involving aged mice showed that five months of daily oral treatment with CA77.1 reduced the buildup of zombie cells in several organs and reduced signs of inflammation and fibrosis. In a separate experiment, treating macrophages isolated from aged mice with CA77.1 restored their ability to engulf particles to levels comparable to those of macrophages from young mice.
The next step was determining whether their findings could be relevant to a human disease associated with aging. A logical candidate was idiopathic pulmonary fibrosis (IPF), in which scar tissue progressively builds up in the lungs, making it increasingly difficult to breathe. People with IPF have a median survival of only three to five years after diagnosis. When the researchers examined lung samples of patients with IPF, they found markedly reduced CMA activity, raising the possibility that a CMA-boosting drug might help against lung fibrosis. They tested CA77.1 in a mouse model of the disease and obtained promising results: Treatment begun early after lung injury reduced the severity of lung fibrosis as well as signs of cellular senescence and inflammation.
Albert Einstein College of Medicine, home to nearly 1,000 M.D., Ph.D., and M.D./Ph.D. students and more than 2,000 full-time faculty members, receives approximately $200M in funding from the National Institutes of Health (NIH) each year and houses six NIH-funded research centers, in cancer, intellectual and developmental disabilities, clinical and translational research, AIDS, and two in diabetes. In partnership with Montefiore Health System, Einstein advances clinical and translational research to accelerate the pace at which new discoveries become the treatments that benefit patients.