Tatsuaki Tsuruyama and Wulamujiang Aini

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/62196

#### **Abstract**

may pave the way for eradicating diseases like cancer. The third provides a summary of the current knowledge about telomere instability induced by anticancer drugs on mammalian cells. The fourth provides a broad evaluation of the associated mechanisms between human health and occupational exposure to different xenobiotics and telomere length, including re‐ cent findings and future perspectives. The fifth discusses the pathophysiological role of shortened telomere length in metabolic and endocrine diseases and the significance of cellu‐ lar senescence. The sixth provides a review of the process by which, in a pathological con‐ text, extratelomeric effects of telomerase are related to the emergence and persistence of the cancer stem cell phenotype. Furthermore, given the common conception of cancer stemness as a major contributor to therapy resistance and tumour relapse, a more complete annota‐ tion of biological mechanisms for its regulation by telomerase will provide the opportunity to develop telomerase-targeted anticancer therapies that kill or differentiate cancer stem cells effectively. Finally, the last chapter reviews hereditary diseases caused by the presence of shortened telomeres, collectively named telomeropathies or telomere biology disorders. In these diseases, cell proliferation is impaired, which results in premature aging and dys‐ function of highly proliferative tissues. Among these diseases are dyskeratosis congenita, Hoyeraal--Hreidarsson syndrome, Revesz syndrome, Coats plus syndromes, aplastic ane‐ mia, idiopathic pulmonary fibrosis, and nonalcholic, noninfectious liver disease, in which mutations present in the genes coding for the components of the telomerase and shelterin complexes and other proteins involved in telomere replication are the cause of these disease. Many researchers have contributed to the publication of this book. Given the fast pace of new scientific publications shedding light on the matter, this book will probably be outdated very soon. We regard this as a positive and healthy fact. The editors hope that this book will continue to meet the expectations and needs of all interested in the telomere/telomerase sci‐ entific field. We now appreciate that these unusual complexes of DNA and proteins we all know as "telomeres" are dynamic and key structures that depend on telomerase and other cellular factors for continuance. Regulation of telomere activity is a dynamic area of current research, and new insights into telomeres and their role in aging and cancer, among other biological functions and pathologies, appear regularly in the scientific world. However, one fact is more than understandable in this difficult biological conundrum: the end of the telo‐

> **Prof. Marcelo L. Larramendy, Ph.D.** Principal Researcher CONICET

> > La Plata, Argentina

School of Natural Sciences and Museum National University of La Plata (UNLP)

mere story is far from being totally unraveled.

X Preface

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. 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 to provide critical data for therapeutic intervention in longterm 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 mecha‐ nisms involved in post-transplant complications including acute cellular rejection, chronic rejection, and chronic hepatitis of unknown cause by ageing and senescence due to telomere shortening.

**Keywords:** Transplantation, liver, telomere
