Mechanism of impairment on liver regeneration in elderly patients: Role of hepatic stellate cell function

Abstract

Japan, along with most other countries in the world, is facing an increasingly aging population with a prolonged life expectancy. Concurrently, the need for medical intervention, including hepatectomy, has also increased for the elderly. Although surgical outcomes for older patients are reported to be comparable with those for younger patients, additional care in the selection of older patients for hepatectomy is considered necessary. Although the effect of aging on human liver regeneration is not fully understood, the regeneration of liver tissue after hepatectomy in elderly patients is shown to be generally worse than in younger patients and, to date, the mechanisms involved in the impairment of liver regeneration have not been fully clarified. Hepatic stellate cells (HSCs) are liver-specific mesenchymal cells that play critical roles in liver physiology and fibrogenesis. Recent studies in liver regeneration have increasingly focused on HSCs rather than on hepatocytes, Kupffer cells, endothelial cells, or infiltrating immune cells and suggest that HSCs might play a critical role in liver regeneration. In this review, we summarize the mechanisms involved in the impairment of liver regeneration in elderly patients, especially focusing on HSCs. We also discuss how HSCs contribute to the impairment of liver regeneration.

Liver regeneration in aged mice: new insights

“…Accordingly, it has been hypothesized that the shorter processes observed in aged HSCs could surround and control the blood flow of fewer sinusoids than in young mice where HSCs encircled more than two sinusoids [ 200 ]. Even if the study of Marcos et al [ 196 ] was not focused on liver regeneration, it provides another possible explanation for the impaired liver regeneration observed in the elderly, as already suggested by Saito et al [ 201 ].…”

Discrepancy between volume and functional recovery in early phase liver regeneration following extended hepatectomy with extrahepatic bile duct resection

“…Although there are many studies investigating liver regeneration after partial hepatectomy, most of these studies evaluated liver regeneration later in the postoperative course (approximately 1 month after resection), and the data on the early phase (1 week after resection) are scarce . Furthermore, all previous reports focused on liver regeneration after hepatectomy “without” extrahepatic bile duct resection (EBR) and the data exclusively focused on the regeneration after extended hepatectomy with EBR are not available.…”

Aging and Cancer: The Waning of Community Bonds

“…Given that random mutations result in the formation of predominantly deleterious allele [ 1 , 46 , 47 , 86 , 87 ], their accumulation in cells during aging will translate into a decrease in functional proficiency, including proliferative and regenerative capacity [ 88 , 89 ]. For example, liver regeneration is delayed in elderly patients [ 90 ] and experimental animals [ 88 ], and this is due, at least in part, to a cell-autonomous decrease in proliferative potential of the aged hepatocyte [ 91 ]. Moreover, it adds to the observation referred to above that the aged liver microenvironment is clonogenic to both normal [ 62 ] and pre-neoplastic [ 63 ] transplanted hepatocytes.…”