**9. Conclusions and future directions**

Studies of age-related disease have mostly focused on telomere length, because excessive telomere shortening leads to diseases such as cardiovascular disease, ulcerative colitis, liver cirrhosis, diabetes, and idiopathic pulmonary fibrosis. Mechanisms of complications (e.g., rejection) of organ transplantation and consequent graft failure related with ageing and senescence are due to telomere shortening. Therefore, studying of telomere length is essential in the field of organ transplantation. Telomere length was negatively associated with patient age, male sex, acute rejection, and fatty liver, and was positively associated with time from transplantation [103]. Our previous study confirmed that accelerated telomere decline in hepatocytes in the first year post-liver-transplantation is presumably due to premature ageing following the acute stress of transplantation and the high rate of cell division that occurs during graft regeneration immediately after transplantation [77]. Accelerated telomere shortening and hepatocyte senescence identified even tolerated human liver allogarfts [104]. The main problem of older donor tissue is its lower ability to endure stress and repair. Preexisting aging may reduce repair and survival capacity, and post-transplant stress such as rejection exhausts further this capacity, leading to graft failure [68]. Ischemia and reperfusion during transplan‐ tation lead to a temporary increase of reactive oxygen species in the organ, which are pre‐ dominant inducers of DNA breaks. Oxidative DNA damage advances telomere shortening [94]. Furthermore, sustained cellular turnover in chronic liver disease accelerates cellular senescence [2-4, 65-66]. The confluence of acute stress, oxidative stress, ageing, and senescence suggests possible mechanisms leading to graft failure. Avoidance of factors associated with oxidative stress and telomere dysfunction is recommended in association with current liver transplantation techniques. Telomeres in grafted livers may elongate somewhat longer if the grafts are immunologically well controlled [105]. Taken together, telomere length is one of the available indicators for evaluation of liver allograft status (Fig.1).

**Figure 1.** Allograft failure and telomere dysfunction
