Telomere reduction in human liver tissues with age and chronic inflammation

Aikata, Hiroshi; Takaishi, Hideki; Kawakami, Yoshiiku; Takahashi, Shoichi; Kitamoto, Mikiya; Matsumoto, Akiko; Onishi, Yaka; Nakanishi, Toshio; Kajiyama, Goro; Ide, Toshinori

doi:10.1016/s0016-5085(00)85756-x

Cited by 60 publications

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“…A previous study reported that the telomere length in the liver is shortened, not only with the progression of fibrosis staging, but also with aging (13). Moreover, the reduction of telomere length has been reported to increase the risk of HCC (14).…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics of hepatocellular carcinoma in elderly patients

Miyaaki

2011

Oncol Lett

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Abstract. The incidence of hepatocellular carcinoma (HCC) in elderly patients in Japan has been on the increase. The aim of the present study was to evaluate the impact of aging on the clinicopathological findings and the survival of HCC patients. A total of 624 patients with HCC were examined in this study. The patients were classified according to their age at the time of diagnosis: one group comprised younger patients (<75 years; n=544) and the second comprised elderly patients [(≥75 years; n=80, (12%)]. Results showed that there were significantly more female patients (younger:elderly, 22:36; p= 0.005), normal livers (younger:elderly, 0.3:6%; p= 0.0002), non-viral HCC (younger:elderly, 11:31%; p<0.001) and solitary tumors (younger:elderly, 53:76%; p= 0.0008) in the elderly group. Five out of seven (71%) non-B non-C (NBNC) HCC patients who developed HCC in the normal liver were elderly patients. Survival between the younger and elderly HCC groups was not significantly different (younger:elderly, 4.38:3.45 years; p= 0.665). Additionally, elderly HCC patients had fewer tumors, more mild underlying liver damage, and more frequent NBNC HCC. Their prognosis was not necessarily poorer than that of the younger HCC patients. Additionally, it appears that elderly patients develop HCC even without fibrosis. Therefore, aging may be a factor affecting hepatocarcinogenesis. IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers (1,2), with an estimated half a million cases annually, worldwide. Although HCC is generally diagnosed in middleaged and elderly individuals, the age distribution of HCC varies according to etiology. The differences in age at the time of diagnosis of HCC affect the treatment strategy.The Japanese population has one of the longest average life spans, and the size of the aged population has been increasing rapidly. As a result, the prevalence of elderly patients with HCC has increased (3-5). There is some controversy regarding whether aging plays a role in the factors and survival of patients with HCC. Previous studies reported that the longterm survival of younger HCC patients is similar to that of elderly patients (6,7). On the other hand, it has been reported that elderly HCC patients tended to have a poorer prognosis (8).A recent increase in the number of elderly HCC patients in Japan has been reported (4,9,10). However, the impact of aging on the emergence of HCC has yet to be adequately investigated. Therefore, the aim of the present study was to investigate the effect of aging on the clinicopathological findings and the survival of HCC patients. Patients and methods Patients.A total of 624 patients presenting with HCC at the Department of Gastroenterology and Hepatology, Nagasaki University School of Medicine, Japan, were recruited for this study, between October 1981 and October 2007. The diagnosis of HCC was based on α-fetoprotein (AFP) levels, des-γ-carboxy prothrombin (DCP) levels, imaging studies including ultrasonography (USG), computerized tomography (CT), magnetic...

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics of hepatocellular carcinoma in elderly patients

Miyaaki

2011

Oncol Lett

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“…Given that telomere shortening and/or impaired telomerase activity have been linked to the development of progressive fibrosis in chronic liver injury [9][10][11][12], it is likely that enhanced telomerase activity serves a protective function. One means by which telomerase may confer protection during chronic liver injury is through the prevention of telomere shortening with its resultant replicative arrest and senescence.…”

Section: Discussionmentioning

confidence: 99%

“…This concept is supported by studies demonstrating that the telomeres of chronically diseased human livers are shorter than those of age-matched controls [9][10][11] Although relatively little work has been done examining the effects of liver injury on telomeres in experimental animals, the available data are intriguing. For example, mice with a targeted deletion of one of the components of telomerase demonstrate impaired hepatic regeneration and accelerated fibrogenesis in the context of liver injury [12].…”

Section: Introductionmentioning

confidence: 98%

Increased hepatic telomerase activity in a rat model of iron overload: A role for altered thiol redox state?

Brown

Mathahs²,

Broadhurst³

et al. 2007

Free Radical Biology and Medicine

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Telomeres are repeated sequences at chromosome ends that are incompletely replicated during mitosis. Telomere shortening caused by proliferation or oxidative damage culminates in replicative arrest and senescence, which may impair regeneration during chronic liver injury. While the effects of experimental liver injury on telomeres have received little attention, prior studies suggest that telomerase, the enzyme complex that catalyzes the addition of telomeric repeats, is protective in some rodent liver injury models. Thus, the aim of this study was to determine the effects of iron overload on telomere length and telomerase activity in rat liver. Mean telomere lengths were similar in ironloaded and control livers. However, telomerase activity was increased 3-fold by iron loading with no change in levels of TERT mRNA or protein. Because thiol redox state has been shown to modulate telomerase activity in vitro, hepatic thiols were assessed. Significant increases in GSH (1.5-fold), cysteine (15-fold), and glutamate cysteine ligase activity (1.5-fold) were observed in iron-loaded livers, while telomerase activity was inhibited by treatment with N-ethylmaleimide. This is the first demonstration of increased telomerase activity associated with thiol alterations in vivo. Enhanced telomerase activity may be an important factor contributing to the resistance of rodent liver to ironinduced damage.

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“…It was originally described in terms of exhaustion of the replicative capacity of cultured primary fibroblasts (3) and was thought to be due in part to telomere attrition (the gradual loss of DNA at the ends of chromosomes that accompanies continuous cell division) (9,10). It has been shown that telomere attrition generates a persistent DNA damage response, which initiates and maintains senescent growth arrest (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Erratum to: From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes

et al. 2016

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The BMB Reports would like to correct in the reference of BMB Rep. 48(10), 549-558 titled "From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes". The REFERENCE should be corrected as red highlighting in this pages. This Erratum's doi is https://doi.org/10.5483/ BMBRep.2016.49.11.122. Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

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Telomere reduction in human liver tissues with age and chronic inflammation

Cited by 60 publications

References 0 publications

Clinical characteristics of hepatocellular carcinoma in elderly patients

Clinical characteristics of hepatocellular carcinoma in elderly patients

Increased hepatic telomerase activity in a rat model of iron overload: A role for altered thiol redox state?

Erratum to: From cell senescence to age-related diseases: differential mechanisms of action of senescence-associated secretory phenotypes

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