Researchers Uncover Mechanism of Aging Spread Through the Bloodstream
A study finds that HMGB1 protein plays a key role in the systemic spread of aging through the bloodstream.
Complete the form below to unlock access to ALL audio articles.
A study led by researchers at Korea University’s College of Medicine has uncovered a mechanism through which cellular aging can spread to distant tissues via the bloodstream. The findings identify a redox-sensitive form of a protein called High Mobility Group Box 1 (HMGB1) as a mediator of this systemic transmission of senescence.
High Mobility Group Box 1 (HMGB1)
HMGB1 is a non-histone DNA-binding protein that regulates transcription inside cells. When released extracellularly, it acts as a signaling molecule.
Redox-sensitive isoform
A redox-sensitive isoform is a variant of a protein whose structure and function are influenced by the balance of reducing and oxidizing conditions.Senescent cells accumulate with age and secrete a range of pro-inflammatory and signaling molecules known collectively as the senescence-associated secretory phenotype (SASP). These factors can induce nearby cells to also enter senescence, a process known as paracrine senescence. While this localized effect is well established, the systemic spread of senescence has been less understood.
Senescence-associated secretory phenotype (SASP)
SASP refers to the suite of molecules secreted by senescent cells, including inflammatory cytokines, chemokines, growth factors and proteases.The research, published in Metabolism – Clinical and Experimental, demonstrates that a reduced form of HMGB1 (ReHMGB1) circulates in the blood and triggers senescence in remote tissues. This isoform, which differs from its oxidized counterpart (OxHMGB1), was shown to promote senescence in various human cell types, including fibroblasts, renal epithelial cells and skeletal muscle cells.
Experimental findings from cell cultures and mouse models
In experiments using cultured cells, ReHMGB1 was found to induce senescence-associated markers and phenotypic changes, while OxHMGB1 did not produce similar effects. These findings were consistent across multiple cell types.
In vivo, mice treated with systemic ReHMGB1 displayed increased expression of senescence markers such as p21 and p16, elevated levels of SASP factors, and impaired skeletal muscle function. These effects suggest that ReHMGB1 may contribute to age-related functional decline.
Blocking HMGB1 improves tissue regeneration in mice
Further experiments using a muscle injury model in middle-aged mice demonstrated that administration of antibodies targeting HMGB1 resulted in lower expression of senescence markers. These mice also showed improved muscle regeneration and enhanced physical performance, compared to untreated controls.
“This study reveals that aging signals are not confined to individual cells but can be systemically transmitted via the blood, with ReHMGB1 acting as a key driver,” said Professor Jeon.
“By blocking this pathway, we were able to restore tissue regenerative capacity, suggesting a promising strategy to treat aging-related diseases.”
This suggests that therapeutic targeting of extracellular HMGB1 could potentially limit the systemic spread of senescence and improve tissue function in the context of aging.
Reference: Shin JW, Jang DH, Kim SY, et al. Propagation of senescent phenotypes by extracellular HMGB1 is dependent on its redox state. Metabolism. 2025;168:156259. doi: 10.1016/j.metabol.2025.156259
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.
This content includes text that has been generated with the assistance of AI. Technology Networks' AI policy can be found here.
