Blood Aging Process Could Be Connected to This Protein Reveal
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A new study has shed light on a protein called Reduced High Mobility Group Box 1 (ReHMGB1) and its role in promoting cellular aging and inflammation. This protein acts as a pro-aging signal that spreads senescence from aging cells to healthy ones, contributing to the aging process.
ReHMGB1 is released extracellularly from stressed or senescent cells, where it acts as a signalling molecule that accelerates aging processes in neighbouring cells. This creates a self-propagating cycle: aging cells secrete more ReHMGB1, which causes additional cells to become senescent.
The Korean team, who conducted the study, demonstrated this role of ReHMGB1 in animal studies. Young mice injected with ReHMGB1 developed aging-like symptoms rapidly, including increased senescence markers and systemic inflammation. On the other hand, treating older mice with antibodies that block HMGB1 signalling can reduce inflammation, improve tissue healing, and enhance physical performance.
The potential strategies to target ReHMGB1 for anti-aging therapies focus on blocking its signalling, modulating its redox state, and reducing circulating ReHMGB1 levels. These approaches hold promise in preclinical models for slowing or reversing age-related tissue damage, inflammation, and functional decline, representing novel targets for anti-aging drug development.
However, it's important to note that ReHMGB1 is unstable in the bloodstream and difficult to target precisely, requiring a treatment that is safe enough to block harmful forms of HMGB1 without interfering with its normal, essential roles.
ReHMGB1 binds to a receptor called RAGE, triggering inflammatory signalling pathways JAK/STAT and NF-κB that reinforce senescence and inflammation. Mice treated with HMGB1 antibodies also showed stronger muscle regeneration and improved grip strength and endurance.
Injections of ReHMGB1 in young mice led to elevated senescence markers in muscles, liver, and other tissues, along with reduced muscle performance. Conversely, administering antibodies that neutralized HMGB1 to middle-aged mice with muscle injuries resulted in fewer senescent cells in muscle tissue.
The hallmarks of senescence include stopping cell division, activating genes such as p16 and p21, and producing inflammatory factors like interleukin-6. Blocking either the RAGE receptor or the JAK/STAT and NF-κB signalling pathway reduced the damage caused by ReHMGB1.
The findings were reported in the journal Metabolism, suggesting a possible therapy to slow the systemic spread of aging. However, the leap from mouse models to human medicine is considerable. The study adds weight to an emerging view of aging as a coordinated process driven by signals that travel through the body.
Senescent cells release a cocktail of substances called the senescence-associated secretory phenotype (SASP), which can damage nearby healthy cells. Only the reduced form of HMGB1, ReHMGB1, is capable of triggering senescence in cells far from where it was released. In older mice, ReHMGB1 levels in the blood were naturally higher than in younger ones.
In conclusion, ReHMGB1 is a key extracellular mediator of cellular aging and inflammation that propagates senescence between cells, and targeting its signalling pathways offers promising anti-aging therapeutic potential. This insight provides a molecular basis for aging as a contagious or spreading process among cells.
- The new study in the journal Metabolism suggests that ReHMGB1, a protein involved in cellular aging and inflammation, could be a target for future health-and-wellness research focused on anti-aging therapies.
- In animal studies, ReHMGB1 was shown to promote aging processes and inflammation, as evidenced by increased senescence markers and systemic inflammation in young mice injected with ReHMGB1.
- The science behind HMGB1 signalling pathways, particularly its binding to the RAGE receptor and the resulting inflammatory signalling cascades (JAK/STAT and NF-κB), could hold keys to future medicine and health, with potential applications in healing, health, and even aging.
- As the Korean team's research demonstrates, understanding the role of ReHMGB1 in aging processes and inflammation could lead to significant breakthroughs in the science of health and wellness, with potential implications for the treatment of aging-related diseases and the promotion of overall health and longevity.
