Abstract
Age is one of the key risk factors to develop malignant diseases leading to a high incidence of hepatic tumors in the elderly population. The only curative treatment for hepatic tumors is surgical removal, which initiates liver regeneration. However, liver regeneration is impaired with aging, leading to an increased surgical risk for the elderly patient. Due to the increased risk, those patients are potentially excluded from curative surgery. Aging impairs autophagy via lipofuscin accumulation and inhibition of autophagosome formation. Autophagy is a recycling mechanism for eukaryotic cells to maintain homeostasis. Its principal function is to degrade endogenous bio-macromolecules for recycling cellular substances. A number of recent studies have shown that the reduced regenerative capacity of the aged remnant liver can be restored by promoting autophagy. Autophagy can be activated via multiple mTOR-dependent and mTOR-independent pathways. However, inducing autophagy through the mTOR-dependent pathway alone severely impairs liver regeneration. In contrast, recent observations suggest that inducing autophagy via mTOR-independent pathways might be promising in promoting liver regeneration. Conclusion: Activation of autophagy via an mTOR-independent autophagy inducer is a potential therapy for promoting liver regeneration, especially in the elderly patients at risk.
Highlights
Iimuro [58] observed that blocking Nuclear factor kappa B (NF-kB) by a NF-kB inhibitor (Ad5IkB) during liver regeneration caused a large number of hepatocytes to undergo apoptosis, indicating that NF-kB plays a positive role in preventing apoptosis during the course of liver regeneration
Aging-related changes lead to decreased autophagy activity, which is an important cause for insufficient liver regeneration
Evidence is accumulating that the modulation of autophagy via pharmacological intervention is an effective approach to promote liver regeneration
Summary
With the advancement of the health system, the lifespan of the population has increased significantly compared with the 1950s [1]. The regenerative capacity of the aging liver is significantly reduced compared with the young liver [5,6]. This age-related change has brought a dilemma to the clinical treatment of liver tumors in this subgroup of patients. The mitotic capacity of the hepatocytes gradually declines with aging, leading to an impairment of liver regeneration in the elderly [6,7]. This impairment represents an additional risk for elderly patients, thereby possibly excluding these patients from curative surgery. Aging is often associated with similar morphological changes such as increased liver steatosis and fibrosis [10], which further limits the functional capacity of the aged remnant liver
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