Scientists at Korea University have identified for the first time a molecular mechanism that explains one of the most mysterious phenomena in biology — how aging cells can spread from one part of the body to another, like an infection. This accelerates the general wear and tear of the body, informs Metabolism.
In the study, it was found that the HMGB1 protein acts as a kind of “mediator of aging” capable of transmitting signals that cause healthy cells to go into a state of aging. At the same time, its influence depends on the chemical state — in particular, on the level of oxidation. Normally, this protein is located in the cell nucleus and performs a structural function in relation to DNA. However, under the influence of stress or with age, the cell releases HMGB1 into the intercellular environment.
Researchers at Korea University have found that it is the “restored” form of HMGB1 (which has not been significantly affected by oxygen) that is able to trigger aging processes by binding to the RAGE receptor and activating the corresponding pathways. The oxidized form of the protein loses this activity and does not cause changes in healthy cells.
In laboratory experiments on human lung, skin, muscle and kidney cells, it was shown that treatment with a reduced form of HMGB1 caused the cells to stop dividing, activate the genes p21 and p16 — markers of aging — and produce inflammatory molecules. No such changes occurred in the cells that interacted with the oxidized protein.
These discoveries open new horizons for antiaging medicine. In particular, it is possible to create drugs that block the interaction of HMGB1 with the RAGE receptor, stimulate its oxidation to an inactive form, or inhibit the inflammatory signaling pathways that are activated by this protein. What’s more, there are already drugs that affect the JAK pathway (known for treating autoimmune diseases) that are also able to prevent HMGB1-induced cellular senescence.
The study changes the very concept of aging in biology: now it is not considered as an isolated process in each cell, but as a transmitted signal capable of spreading between tissues. The reconstituted HMGB1 has been identified as a “progeronic factor”—that is, a substance that promotes aging. At the same time, it can become a promising target for therapeutic intervention. For those who dream of a healthy and active longevity, this protein can be both the cause of problems and the key to solving them.
