Telomere Reduction in Human Liver Tissues with Age and Chronic Inflammation

doi:10.1006/excr.2000.4862

Experimental Cell Research

Volume 256, Issue 2, 1 May 2000, Pages 578-582

https://doi.org/10.1006/excr.2000.4862 Get rights and content

Abstract

Telomere shortening in human liver with aging and chronic inflammation was examined by hybridization protection assay using telomere and Alu probes. The reduction rate of telomere repeats in normal liver (23 samples from patients 17–81 years old) was 120 bp per year, which is in good agreement with the reported reduction rate in fibroblasts of 50–150 bp at each cell division and replacement rate of human liver cells, once a year. Mean telomere repeat length shortened to about 10 kbp in normal livers from 80-year-old individuals. The number of telomere repeats in chronic hepatitis (26 samples) and liver cirrhosis (11 samples) was significantly lower than that in normal liver of the same age (P < 0.01). Telomere length in all these chronic liver disease samples, other than two exceptions, was not reduced shorter than 5 kbp, which was assumed to give a limit of proliferation (Hayflick's limit) to untransformed cells.

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Cited by (144)

Is telomere length in buccal or salivary cells a useful biomarker of exposure to air pollution? A review
2022, Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Citation Excerpt :
Household air pollution may influence TL by increasing the replication rate of cells and by enhancing the extent of telomere loss during each replication. Fine PM emitted from biomass combustion has a high intrinsic oxidative potential and inflammatory properties [47,48], which has been shown to accelerate telomere shortening in in vitro and human studies [49,50]. In the present review, shorter TL of buccal cells was associated with PM2.5 and black carbon exposure in women using biomass stoves for home use [32], confirming the results of a previous feasibility study [31], in which higher exposed women had a buccal TL reduced by 43% compared to the low exposure group.
Telomeres are repetitive DNA-protein sequences located at the end of chromosomes and play an essential role in preserving information in our genome by protecting against end-to-end fusion, nucleolytic degradation, breakage, and inappropriate recombination. The telomeres shorten with aging and this process can be affected by oxidative stress and inflammation. Environmental and occupational factors may contribute to telomere length (TL) shortening, as demonstrated by an increasing number of studies. In particular, air pollution was associated with aging-related health outcomes and molecular alterations, such as telomeric shortening. Leukocytes are widely used for TL measurement. However, buccal and salivary cells have more intimate contact with airborne pollutants and are easier to sample.
The objective of this review was to identify whether salivary or buccal TL represents a valid marker for evaluating the effects of pollution on health. The reviewed studies investigated the association between TL and occupational exposure (genotoxic substances in mechanical workers, and pesticides in pesticides applicators), residential traffic exposure (NO_x, NO₂, PM_2.5, PM₁₀, and black carbon), and household air pollution (PM_2.5 and black carbon from biomass stoves). The studies involved adults and children. Although few studies have yet been carried out, almost all reported a negative association between salivary or buccal TL and exposure to air pollutants stating that it could be a good indicator of occupational or airborne pollution exposure. However, further research is needed to evaluate the effect of acute versus long-term exposure on salivary or buccal TL as well as the role of confounding factors. Moreover, most of the reviewed studies were conducted on healthy adults, so it is important to deeply investigate how TL is associated with all-cause mortality such as cancer, diabetes, cardiovascular disease, and respiratory disease, how it can be affected during childhood, and which changes over time can be associated with diseases’ onset in adulthood.
Cellular senescence during aging and chronic liver diseases
2022, Cellular Senescence in Disease
Cellular senescence is a cell fate characterized by an irreversible cell-cycle arrest, and among various changes, metabolic dysfunction and a proinflammatory secretory phenotype. Senescence has attracted a lot of interest in recent years, particularly, because of its role as a driver of aging and disease.
Senescence has been found in different cell types in the liver, including hepatocytes, cholangiocytes, and hepatic stellate cells. Cellular senescence has been associated with several diseases such as nonalcoholic and alcoholic fatty liver disease, chronic hepatitis, liver cancer, chronic biliary liver disorders, and hereditary hemochromatosis. Importantly, studies have shown that clearance of senescent cells improves phenotypes in preclinical models during aging and disease, supporting the hypothesis that senescent cells may be promising targets for interventions to counteract chronic liver diseases.
This chapter focuses on senescence in aging and chronic liver disease and explores some of the underlying molecular mechanisms and therapeutic opportunities.
The impact of oxidative DNA damage and stress on telomere homeostasis
2019, Mechanisms of Ageing and Development
Telomeres are dynamic nucleoprotein-DNA structures that cap and protect linear chromosome ends. Because telomeres shorten progressively with each replication, they impose a functional limit on the number of times a cell can divide. Critically short telomeres trigger cellular senescence in normal cells, or genomic instability in pre-malignant cells, which contribute to numerous degenerative and aging-related diseases including cancer. Therefore, a detailed understanding of the mechanisms of telomere loss and preservation is important for human health. Numerous studies have shown that oxidative stress is associated with accelerated telomere shortening and dysfunction. Oxidative stress caused by inflammation, intrinsic cell factors or environmental exposures, contributes to the pathogenesis of many degenerative diseases and cancer. Here we review the studies demonstrating associations between oxidative stress and accelerated telomere attrition in human tissue, mice and cell culture, and discuss possible mechanisms and cellular pathways that protect telomeres from oxidative damage.
Stress, cell senescence and organismal ageing
2018, Mechanisms of Ageing and Development
Cellular senescence was first described by Hayflick and Moorhead in the 1960s as the irreversible arrest of cells following prolonged cultivation. Telomere shortening is the key mechanism driving replicative senescence in human fibroblasts. Later, pioneering work by Olivier Toussaint and others showed that stress plays a major role in the induction of senescence in vitro, a phenomenon known as stress-induced premature senescence or SIPS. It is also now widely accepted that senescence plays a role in vivo. An emerging body of evidence from animal models, and particularly mice, has demonstrated an important role for senescence in several processes such as embryonic development, wound healing, tumour suppression and ageing. However, mostly due to a lack of availability of tissues and specific markers, less is known about the importance of cell senescence in humans. In this review, we summarize some of the key findings in the field of senescence, stress-induced senescence and telomeres. We focus particularly on the role of telomere dysfunction and senescence during the ageing process as well as potential interventions, including pharmacological approaches like telomerase activators and senolytics, to counteract their detrimental effects in ageing and disease.
Sphingolipids at the Crossroads of NAFLD and Senescence
2018, Advances in Cancer Research
Nonalcoholic fatty liver disease (NAFLD) is a group of liver disorders encompassing simple hepatic steatosis and its more aggressive forms of nonalcoholic steatohepatitis and cirrhosis. It is a rapidly growing health concern and the major cause for the increasing incidence of primary liver tumors. Unequivocal evidence shows that sphingolipid metabolism is altered in the course of the disease and these changes might contribute to NAFLD progression. Recent data provide solid support to the notion that deregulated ceramide and sphingosine-1-phosphate metabolism are present at all stages of NAFLD, i.e., steatosis, nonalcoholic steatohepatitis, advanced fibrosis, and hepatocellular carcinoma (HCC). Insulin sensitivity, de novo lipogenesis, and the resulting lipotoxicity, fibrosis, and angiogenesis are all seemingly regulated in a manner that involves either ceramide and/or sphingosine-1-phosphate. Sphingolipids might also participate in the onset of hepatocellular senescence. The latter has been shown to contribute to the advancement of cirrhosis to HCC in the classical cases of end-stage liver disease, i.e., viral- or alcohol-induced; however, emerging evidence suggests that senescence is also involved in the pathogenicity of NAFLD possibly via changes in ceramide metabolism.
Applying LASSO logistic regression for prediction of biliary complications after ex-vivo liver resection and autotransplantation in end-stage hepatic alveolar echinococcosis
2023, Research Square

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¹: These authors contributed equally to this work.

²: To whom correspondence and reprint requests should be addressed. Fax: +81-82-257-5294. E-mail: [email protected].

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Experimental Cell Research

Abstract

References (29)

The limited in vitro lifespan of human diploid cell strains

Exp. Cell Res.

The serial cultivation of human diploid cell strains

Exp. Cell Res.

Studies on the molecular-genetic basis of replicative senescence in Werner syndrome and normal fibroblasts

Exp. Gerontol.

Human endothelial cell life extension by telomerase expression

J. Biol. Chem.

Exp. Cell Res.

Telomerase activity and telomere length in hepatocellular carcinoma and chronic liver disease

Gastroenterology

Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis

Cancer Genet. Cytogenet.

Telomere shortening in chronic liver diseases

Biochem. Biophys. Res. Commun.

Marginal donors in liver transplantation: The role of donor age

Transplant Proc.

Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype

Lab. Invest.

The relationship between in vitro cellular aging and in vivo human age

Proc. Natl. Acad. Sci. USA

Chronologic and physiologic age affect replicative life-span of fibroblasts from diabetic, prediabetic, and normal donors

Science

Extension of life-span by introduction of telomerase into normal human cells

Science

Telomerase activity is sufficient to allow transformed cells to escape from crisis

Mol. Cell. Biol.

Cited by (144)

Is telomere length in buccal or salivary cells a useful biomarker of exposure to air pollution? A review

Cellular senescence during aging and chronic liver diseases

The impact of oxidative DNA damage and stress on telomere homeostasis

Stress, cell senescence and organismal ageing

Sphingolipids at the Crossroads of NAFLD and Senescence

Applying LASSO logistic regression for prediction of biliary complications after ex-vivo liver resection and autotransplantation in end-stage hepatic alveolar echinococcosis

Rapid CommunicationTelomere Reduction in Human Liver Tissues with Age and Chronic Inflammation

Abstract

Exp. Cell Res.

Exp. Cell Res.

Exp. Gerontol.

J. Biol. Chem.

Exp. Cell Res.

Gastroenterology

Cancer Genet. Cytogenet.

Biochem. Biophys. Res. Commun.

Transplant Proc.

Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype

Lab. Invest.

The relationship between in vitro cellular aging and in vivo human age

Proc. Natl. Acad. Sci. USA

Chronologic and physiologic age affect replicative life-span of fibroblasts from diabetic, prediabetic, and normal donors

Science

Extension of life-span by introduction of telomerase into normal human cells

Science

Telomerase activity is sufficient to allow transformed cells to escape from crisis

Mol. Cell. Biol.

Rapid Communication
Telomere Reduction in Human Liver Tissues with Age and Chronic Inflammation