FIGURE 2.

The proposed role of aging in liver diseases. (A) IRI: Aging livers experience reduced levels of ATG4B and PARKIN, leading to decreased autophagy/mitophagy and increased ROS. Enhanced NF-κB activation in macrophages causes greater inflammation, worsening IRI. (B) DILI: Older adults have decreased liver drug metabolism due to reduced activity of CYP enzymes and lower clearance, along with diminished GSH and SOD levels. These factors, combined with polypharmacy, raise susceptibility to DILI. (C) ALD: Aging diminishes alcohol-metabolizing enzymes and proteostasis mechanisms like autophagy/proteasome. Decreased SIRT1 levels and increased inflammation further exacerbate ALD. (D) MASLD: The aging liver shows elevated necroptosis and ferroptosis proteins, increased lipogenesis, and inflammation, while fatty acid beta-oxidation and autophagy decrease, leading to more severe MASLD. Abbreviations: ADH, alcohol dehydrogenase; ALD, alcohol-associated liver disease; ALDH2, acetaldehyde dehydrogenase 2; CYP, cytochrome; GSH, glutathione; IRI, ischemia-reperfusion injury; MASLD, metabolic dysfunction–associated steatotic liver disease; ROS, reactive oxygen species; SIRT1, sirtuin 1; SOD, superoxide dismutase.