**1. Introduction**

#### **1.1. Summary**

Living-donor liver transplant is a life-saving procedure for people with end-stage liver disease that has increased the number of organs available for people on the liver transplant waiting list. Patients often receive grafts from their relatives in living-donor liver transplantation.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Maintenance of long-term graft function is important in liver transplant recipients. Livers from older donors have worse graft survival rates in human liver transplantation, and therefore, accurate evaluation of graft aging and senescence is expected providing critical data for therapeutic intervention in long-term grafts. Many insults, including rejection, can contribute to post-transplant damage. Late post-transplant biopsies frequently show chronic hepatitis of unknown cause, and this can cause late graft dysfunction leading to cirrhosis. Telomere length in chronic hepatitis or cirrhosis is significantly lower than that in normal livers of the same age. Sustained cellular turnover in chronic liver disease accelerates cellular senescence or a crisis because of telomere shortening. Here, we review the mechanisms involved in posttransplant complications including acute cellular rejection, chronic rejection, and chronic hepatitis of unknown cause by ageing and senescence due to telomere shortening.

#### **1.2. Background**

Telomeres are comprised of tandem nucleotides repeats (TTAGGG) and their functional role includes protection against the degradation of chromosomes and the maintenance of genome integrity and stability [1]. Telomere shortening relates with the etiology of liver allograft dysfunction and/or graft failure such as acute cellular rejection, chronic rejection, and chronic hepatitis of unknown cause (idiopathic post-transplant hepatitis) after liver transplantation. Older people are more sensitive to most acquired liver disorders and are more indefensibly to the consequences of liver disease. In the chronic hepatic injury and inflammation, cellular senescence functions as an essential stress-response mechanism to restrict the proliferation of damaged cells, but this benefit is at the expense of senescence-related organ dysfunction. The dual role of cell senescence in chronic liver disease will make this an intriguing but challenging area for future clinical interventions. In the setting of chronic liver disease, telomere reduction was more significant than in hepatocytes of normal livers of subjects of the same age [2-4]. In this review, we will discuss mechanism of telomere shortening involved in hepatocyte senescence after liver transplantation by examining the present-day knowledge of telomere structure. Particularly, we discuss mechanisms by which inflammation, acute stress, and oxidative stress accelerate cellular senescence.
