Summary: New research has revealed that aging is spread through the bloodstream from one area to another. Redox-sensitive proteins like ReHMGB1, which are secreted by dormant cells, were discovered to be the cause of aging in faraway tissues, preventing regeneration and muscle function.
ReHMGB1 was reduced by biological aging markers and improved physical performance in animals after blocking it with antibodies. These findings provide a potent healing target to slow or stop age-related decline and identify a crucial molecular messenger of widespread aging.
Important Information
- ReHMGB1 transmits senescence impulses from one cell to another.
- Removable Damage: In aging mice, HMGB1-blocking superior tissue repair and function.
- Medical Potential: Eliminating circulating HMGB1 may aid in the treatment of age-related illnesses.
Korea University College of Medicine as a resource
A Korean study team’s first-ever investigation into how biological aging you spread systemically through the bloodstream, providing new insights and possible healing options to fight aging-related decline.
A significant external senescence-associated secretory phenotype ( SASP) issue, High Mobility Group Box 1, according to Professor Ok Hee Jeon’s research team at Korea University’s College of Medicine, plays a crucial role in the transmission of aging from aging cell to distant organs.
Sensitive cells are known to produce pro-inflammatory factors and signaling molecules, collectively known as SASP, which cause paracrine aging in nearby cells.
These senescent cells accumulate in numerous tissues over time, causing tissue dysfunction and regenerative capacity to be compromised. The process by which aging spreads centrally remained to be seen, though.
In their most recent study, which was published in the Metabolism , – , Clinical and Experimental ( Impact Factor 10.9, top 4.6 % in endocrinology and metabolism ), Professor Jeon’s team provides the first evidence that reduced HMGB1 ( ReHMGB1 ), a redox-sensitive isoform of HMGB1, circulates through the bloodstream and causes senescence in distant tissues.
The researchers demonstrated that extracellular ReHMGB1, but not its oxidized form ( OxHMGB1 ), effectively induces senescence-like characteristics in a number of human cell types, including fibroblasts, renal epithelial cells, and skeletal muscle cells, using both in vitro and in vivo models.
ReHMGB1-treated mice displayed higher senescence markers ( p21, p16 ), higher expression of SASP factors, and decreased muscle function.
Additionally, the use of anti-HMGB1 antibodies improved tissue regeneration and improved physical performance in a tissue damage design in middle-aged animals.
These findings emphasize the therapeutic potential of utilizing external HMGB1 to treat or prevent age-related cell dysfunction.
ReHMGB1 serves as a key driver in this study, pointing out that aging signals may remain centrally transmitted via the blood.
By preventing this route, we were able to recover muscle regeneration capacity, which is a promising approach to treating aging-related diseases.
Funding: This study received funding from the Myokine Research Center ( MRC ) and the Ministry of Science and ICT’s Mid-sized Research Support Project. and was conducted in partnership with renowned aging science professionals from abroad, including Turfts University Professor Christopher Wiley and Professor Irina Conboy of UC Berkeley.
About this information about aging study
Author: Kihoon Yu
Source: Korea University College of Medicine
Contact: Kihoon Yu – Korea University College of Medicine
Image: The image is credited to Neuroscience News
Start access to original analysis
Okay Hee, JEON, and others cite the statement,” Propagation of dormant phenotypes by external HMGB1 is dependant on its redox state.” Stamina
Abstract
External HMGB1’s dissemination of dormant phenotypes depends on its redox state.
Background andamp; goal
Cellular aging spreads systemically through the blood flow, but its methods are still undetermined. A multifunctional senescence-associated secretory phenotype ( SASP) factor known as High Mobility Group Box 1 ( HMGB1 ) can be found in a variety of redox states. We examine the impact of HMGB1 ( ReHMGB1 ), a redox-sensitive protein, on paracrine and systemic senescence.
Methods
We used the immunomodulatory aging cultured type to test the impact of ReHMGB1 on biological aging. To evaluate widespread aging, both in vitro and in vivo, each redox state of HMGB1 was treated reversibly. RT-qPCR, European wash, and SA-gal &, EdU dyeing, p16INK4a , and p21 expression were used to determine senescence. ReHMGB1-driven regulatory changes and the main pathways were investigated by resulting in a pool of RNA sequencing.
SASP patterns from ReHMGB1-treated cells were characterized by hormone arrays. ReHMGB1 was centrally administered to young mice in vivo to cause senescence across various tissues. Middle-aged mice were used as a tissue damage model to test the HMGB1 blockade’s medical efficacy.
Results
ReHMGB1 from external, but not in its oxidized form, strongly initiated senescence-like behaviors in a variety of mobile types and tissues. RAGE-mediated JAK/STAT and NF-B pathways were activated by genomic analysis, which led to SASP appearance and mobile cycle imprisonment.
Cytokine monitoring demonstrated immunomodulatory aging characteristics brought on by ReHMGB1. ReHMGB1 treatment increased aging markers , in situ, while HMGB1 inhibition decreased senescence, attenuated systemic disease, and increased muscle regeneration.
Conclusion
Redox-dependent pro-geronic component is responsible for structural senescence, known as ReHMGB1. Targeting external HMGB1 may have the ability to be therapeutically effective in preventing aging-related disorders.
