Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver

Abstract

Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS-induced cellular stress and promotes hepatocyte proliferation but may aggravate hepatic fibrosis. Therefore, a well-balanced autophagy modulation strategy might be suitable to alleviate age-related liver dysfunction. Conclusion. Modulation of autophagy is a promising strategy for “rejuvenation” of the aged liver. Detailed knowledge regarding the most devastating processes in the individual patient is needed to effectively counteract aging of the liver without causing obvious harm.

The Emerging Role of Extracellular Vesicles and Autophagy Machinery in NASH—Future Horizons in NASH Management

“…Based on various studies on the impact of the autophagy pathway on NAFLD, it is demonstrated that autophagy is closely associated with NASH progression via several factors that either promote or inhibit the autophagy pathway. The downregulation of autophagy is observed in many circumstances that favor NASH, such as increased insulin levels [ 19 ], obesity [ 20 ], the increased consumption of lipids [ 20 , 21 ], as well as aging [ 22 ] and the overabundance of stored lipids in the liver. The downregulation of the pathway is estimated via the assessment of LC3II and autophagosomes, as well as the number of autophagolysosomes.…”

FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC

“…The transmembrane member 16A (TMEM16A) promotes the ubiquitination and degradation of glutathione peroxidase 4 (GPX4), thereby aggravating HIRI 9 . Due to older livers are more susceptible to lipid disorders and mitochondrial failure as well as iron ions further accumulate in the liver with age, we speculated that older livers are more prone to ferroptosis 10 . However, the role of ferroptosis in older HIRI is still unclear, and revealing the potential regulatory mechanism is critical for developing effective treatments to mitigate HIRI in the older.…”

Berberine enhances autophagic flux by activating the Nrf2 signaling pathway in bovine endometrial epithelial cells to resist LPS‐induced apoptosis

“…Autophagy can control cell fate through distinct crosstalk signals (Xu et al, 2021). In many tissues, protective autophagy can be activated to inhibit cell apoptosis induced by stressors (Maiuri et al, 2007; Xue et al, 2016).…”