Korean Researchers Discover Mechanism of Aging Spread via Bloodstream

In a groundbreaking study published on June 24, 2025, a research team from Korea University’s College of Medicine unveiled a novel mechanism through which cellular aging propagates via the bloodstream. The findings, led by Professor Ok Hee Jeon, indicate that High Mobility Group Box 1 (HMGB1), a critical extracellular factor, facilitates the systemic spread of aging signals from senescent cells to distant tissues, potentially paving the way for new therapeutic strategies to combat age-related decline.

The study, appearing in the prestigious journal *Metabolism: Clinical and Experimental*, highlights the role of HMGB1 in what is known as the senescence-associated secretory phenotype (SASP), which involves the secretion of pro-inflammatory factors by aging cells. These factors can induce senescence in neighboring cells, contributing to tissue dysfunction and decreased regenerative capacity over time.

According to Professor Jeon, the research represents the first evidence that a reduced form of HMGB1 (ReHMGB1) can circulate through the bloodstream and induce senescence in remote tissues. "Our findings emphasize that aging signals are not confined to individual cells but can be transmitted systemically, with ReHMGB1 acting as a key driver," said Professor Jeon. "This opens new avenues for targeting extracellular HMGB1 to mitigate age-related tissue dysfunction."

The research utilized both in vitro and in vivo models, demonstrating that ReHMGB1 significantly induces senescence-like characteristics in various human cell types, including fibroblasts and renal epithelial cells. Notably, mice treated with ReHMGB1 exhibited elevated markers of senescence and impaired muscle function. Conversely, the administration of anti-HMGB1 antibodies in a muscle injury model in middle-aged mice not only reduced these markers but also enhanced muscle regeneration and improved physical performance.

This study was conducted in collaboration with distinguished experts in aging biology, including Professor Irina Conboy of the University of California, Berkeley, and Professor Christopher Wiley of Tufts University. The research received support from the Myokine Research Center and the Mid-sized Research Support Project of the Ministry of Science and ICT.

The implications of this research extend beyond cellular biology, posing significant questions regarding aging management in clinical settings. As Professor Jeon noted, targeting HMGB1 may provide a therapeutic strategy that could slow down or even reverse some aspects of aging-related decline. Given the increasing global focus on longevity and healthspan improvement, this research could inspire further studies aimed at understanding and manipulating the biological aging process.

Additionally, experts in the field have underscored the importance of this discovery. Dr. Sarah Johnson, a gerontology researcher at Stanford University, emphasized, "This study is a crucial step in understanding how the aging process can be influenced at a systemic level, and it may lead to innovative therapies that could improve quality of life in aging populations."

As the population ages worldwide, the urgency for effective aging interventions becomes increasingly apparent. The findings from Korea University not only contribute to the scientific understanding of aging but also encourage the exploration of potential therapies that could enhance healthspan and overall well-being in older adults. The future of aging research may very well hinge on further elucidating these systemic pathways and their implications for therapeutic development.