Aging-Associated Gsk3Β Overexpression Exacerbates Hepatic Ischemia-Reperfusion Injury Through Nrf2 Deficiency-Induced Hepatocyte Ferroptosis
As we age, our bodies undergo various changes, and sometimes these changes can make us more vulnerable to certain health issues. One such issue is liver damage that can occur when the liver’s blood supply is temporarily cut off and then restored, a process known as ischemia-reperfusion injury. This type of injury is a significant concern during liver surgeries or transplantations, especially in older patients.
New research sheds light on why aging livers are more susceptible to this damage. Scientists discovered that in older livers, there’s an overabundance of a protein called GSK3β. This excess GSK3β, in turn, leads to a shortage of another crucial protein, Nrf2. Think of Nrf2 as a cellular bodyguard, responsible for activating the body’s natural defenses against harmful molecules.
When Nrf2 is deficient, liver cells lose their protective shield, making them vulnerable to a unique form of cell death called ferroptosis. Unlike other types of cell death, ferroptosis is characterized by an accumulation of iron and damage to the fats within cell membranes. This cascade of events—increased GSK3β, reduced Nrf2, and subsequent ferroptosis—significantly worsens the liver damage experienced during ischemia-reperfusion injury.
Understanding this intricate pathway opens up new possibilities for protecting aging livers. By targeting GSK3β or boosting Nrf2 activity, or even directly inhibiting ferroptosis, we might be able to develop new treatments to safeguard the livers of elderly patients undergoing procedures that carry a risk of this type of injury.
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