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ANTI-AGING / PROTEIN
WHY WE AGE ... SPECIFIC PROTEIN SETS OFF "CHEMICAL REACTION"
from the desk of Joseph Patrick Jakubal
Aging spreads through the body like an infection, and a "protein" has been implicated.
Scientists have discovered how a Redox Switch turns youthful cells old (and how to stop it)
SEOUL, South Korean researchers have identified a molecular culprit behind one of
the most puzzling phenomena in biology, i.e., how cellular aging spreads from one part of the body to
another, potentially accelerating the overall aging process.
A new study published in the journal "Metabolism" reveals that a protein called
HMGB1 acts as a redox-sensitive aging messenger carrying signals that can turn healthy cells
into aged, dysfunctional ones ... however only when it is in the right chemical state.
HOW "HMGB1 PROTEIN" CONTROLS CELLULAR AGING
HMGB1 normally resides inside the nucleus of cells, where it helps organize DNA.
But when cells become stressed or aged, a state scientists call senescent. The cells then release
this protein into their surroundings. Once outside the cell, HMGB1 can alter it's chemical form depending
on how much oxygen it has been exposed to.
The research team from Korea University College of Medicine discovered that only a
"reduced" form of HMGB1 acts as an aging accelerator. Much like how rust depends on environmental conditions,
the chemical surroundings determine whether this protein triggers damage. The reduced form, which has
not been exposed to much oxygen, can bind to cellular receptors and activate aging pathways.
The oxidized form, by contrast, loses this ability.
To test this, the researchers conducted extensive lab experiments using human lung, kidney,
skin, and muscle cells. When treated with the reduced form of HMGB1 for several days, healthy cells began showing classic
signs of aging ... they stopped dividing, expressed senescence markers like p21 and p16, and began releasing inflammatory
molecules.
Cells treated with the oxidized form remained healthy and continued to divide normally.
The effect was consistent across all tested cell types.
"Senescent cells" accumulate as we age ... CAR T cells can be programmed to seek them out and
destroy them. Pancreatic tissue samples from an old mouse treated with CAR T cells became young.
WHY CHEMICAL STATE DETERMINES AGING EFFECTS
Advanced genetic sequencing revealed what was happening inside the cells. The reduced form of
HMGB1 activated molecular signaling cascades, specifically the JAK/STAT and N-κB pathways, that are known to promote
inflammation and cellular aging.
When researchers blocked these pathways with existing drugs, the aging effects were
eliminated, confirming that the reduced form acts through these mechanisms. According to the study,
Extracellular ReHMGB1 (but not its oxidized form) robustly induced senescence-like phenotypes across multiple cell
types and tissues.
This creates a potentially harmful cycle: as people age and accumulate more senescent cells,
those cells release more reduced HMGB1, which then causes even more healthy cells to become senescent. In this way, aging
may propagate through the body via molecular messengers.
MOUSE STUDIES REVEAL POTENTIAL ANTI-AGING THERAPIES
The team found that these cellular effects translated into real-world consequences in animals. When young, healthy mice
were injected with the reduced form of HMGB1 at a dose of 5 mg per kilogram of body weight, the animals developed
aging-like symptoms within one week. Muscle tissue showed elevated levels of senescence markers, and blood tests
revealed a spike in inflammatory cytokines linked to aging.
In a separate experiment, 15-month-old mice with muscle injuries were treated with antibodies
that block HMGB1. Compared to untreated mice, those receiving the antibody showed better muscle healing, reduced
inflammation, and improved physical performance. They gripped harder, ran farther on treadmills, and healed faster,
indicating that interfering with HMGB1 signaling helped reduce age-related dysfunction.
Blood samples from older human adults (ages 70 - 80) also contained significantly higher levels of
the reduced form of HMGB1 compared to people in their 40s. Similar age related increases were seen in laboratory mice.
FUTURE APPLICATIONS FOR HUMAN ANTI-AGING APPLICATIONS FOR HUMAN ANTI-AGING MEDICINE
The findings open several potential avenues for anti-aging therapies. Drugs could be developed to block the reduced form of
HMGB1 from binding to its receptor (called RAGE), to promote its oxidation into an inactive form, or to block the
inflammatory pathways it activates.
Some of these strategies may already be feasible. The study showed that Momelotinib,
an existing JAK2 inhibitor approved for treating myelofibrosis (a type of bone marrow cancer) can prevent HMGB1-induced
aging in cells.
This research shifts how scientists understand aging. Rather than being an isolated process
occurring independently in each cell, aging may spread through tissues and organs via chemical messengers. The study
describes the reduced form of HMGB1 as a pro-geronic factor - a molecule that promotes aging - and highlights it as
a promising target for future therapies.
For anyone hoping to age more gracefully, this protein may hold the key to both the problem and future therapeutic strategies.
Disclaimer: The findings described in this article are based on laboratory and animal studies. While promising, they have
not yet been tested in clinical trials for anti-aging purposes in humans. Always consult qualified medical professionals
before considering experimental therapies.
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