A single protein can trigger a chain reaction of aging in the body

Normally, HMGB1 is located in the cell nucleus and participates in the organization of DNA. However, when cells experience stress or age — they become so—called senescent – they release HMGB1 outside. And this is where the main thing begins.: As scientists have found out, only the reduced form of this protein, which has not undergone oxidation, has the ability to trigger aging in healthy cells. This form interacts with receptors on the cell surface and activates molecular chains associated with inflammation and aging, such as the JAK/STAT and NF-kB pathways.

To test their hypothesis, the scientists conducted experiments on human lung, kidney, skin, and muscle cells. When restored HMGB1 was added to the nutrient medium, healthy cells began to show signs of aging: they stopped dividing, accumulated characteristic markers of senescence, and began to secrete inflammatory molecules. At the same time, the cells treated with the oxidized form of the protein continued to function normally.

Experiments on mice have confirmed the dangerous potential of the protein. Restored HMGB1 was injected into young animals, and within a week they showed clear signs of aging: deterioration of muscle tissue, an increase in inflammatory proteins in the blood, and a general decrease in physical activity. But when elderly mice with injuries were injected with antibodies that block HMGB1, the effect was the opposite — tissue repair improved, inflammation decreased, and physical fitness improved markedly.

Additional blood tests showed that the level of the restored form of HMGB1 is significantly higher in the elderly (aged 70-80 years) than in middle-aged people. The same age-related protein growth was observed in laboratory mice.

In the future, drugs may be developed that either block HMGB1 itself, prevent it from activating its receptors, or direct it to an inactive, oxidized form. Moreover, existing drugs that affect the JAK/STAT pathway (for example, those used in autoimmune diseases) have shown effectiveness in suppressing the effects of HMGB1 in the laboratory.

The study offers a new perspective on the aging process itself. It can be not just an accumulation of damage in each individual cell, but a systemic, transmissible process — almost like inflammation or infection. If this is true, then perhaps we are on the verge of creating the first therapy capable of slowing aging at the level of the entire body.