Scientists Discover Key to Reversing Immune System Aging with Platelet Factor 4
A groundbreaking new study reveals that restoring levels of a declining protein, platelet factor 4, can rejuvenate aging blood and immune cells, offering a potential pathway to combat age-related disorders.
As we age, the visible signs – graying hair and weakening muscles – are accompanied by a decline in immune function. This deterioration stems, in part, from changes within hematopoietic stem cells, the rare and vital cells residing in bone marrow responsible for generating blood and immune cells. These stem cells are so crucial that researchers often refer to them as “the Holy Grail of the immune system.”
Researchers at the University of Illinois Chicago (UIC) have pinpointed a key mechanism driving this aging process: the diminishing presence of platelet factor 4 (PF4). Their findings, published in the journal Blood in July 2025, demonstrate that replenishing PF4 levels can reverse signs of aging in both mice and human cells.
In a young, healthy body, hematopoietic stem cells efficiently produce two primary types of blood cells: myeloid cells, which include red blood cells and certain immune cells, and lymphoid cells, encompassing the crucial T and B cells that defend against infection. However, with age, these stem cells increasingly favor myeloid cell production, leading to a reduction in the number of protective lymphoid cells. This shift compromises the immune system’s effectiveness. “That’s one of the reasons why, normally, older individuals are not used as donors for bone marrow transplantation, because their stem cells are not as potent,” one researcher explained.
The UIC team discovered that PF4 acts as a critical regulator, particularly for myeloid cell production. In youth, PF4 signals hematopoietic stem cells to curb excessive multiplication, preventing uncontrolled proliferation. As PF4 levels decline with age, these stem cells begin to divide more frequently, increasing the risk of accumulating harmful mutations. These mutations can contribute to inflammation, elevate the risk of blood cancers, and even play a role in cardiovascular disease.
Remarkably, the researchers found that administering PF4 to older mice reversed these age-related changes. A month-long regimen of daily PF4 infusions restored the appearance and function of their immune and blood cells to a more youthful state. The same rejuvenating effect was observed when PF4 was added to aging human stem cells in laboratory experiments. “It rejuvenated the aging of the blood system,” a senior official stated.
While PF4 is not a “silver bullet” for reversing all aspects of aging, researchers emphasize its potential as a component of broader rejuvenation strategies. “It’s clear evidence that it’s possible to reverse, intrinsically, certain age-associated disorders,” one researcher noted. The team believes PF4 could be particularly valuable in preventing or improving age-related disorders affecting the blood and immune systems.
The study was led by Sandra Pinho, associate professor of pharmacology and regenerative medicine at the UIC College of Medicine, and Sen Zhang, a postdoctoral fellow in the Pinho lab. Co-leadership was provided by Constantinos Chronis from the Department of Biochemistry and Molecular Genetics. Other contributors included Charles Ayemoba, Anna Di Staulo, Kenneth Joves, Chandani Patel, Eva Leung, Maura Bueno, Xiaoping Du, and Sang-Ging Ong.
Source: University of Illinois Chicago
Journal reference: Zhang, S., et al. (2025). Platelet Factor 4 (PF4) Regulates Hematopoietic Stem Cell Aging. Blood Journal. doi.org/10.1182/blood.2024027432
