Publication Title: 

Aging is characterized by a progressive decline of cellular functions. The aging liver appears to preserve its function relatively well. Aging is associated in human liver with morphological changes such as decrease in size attributable to decreased hepatic blood flow. Ultrastructural analysis of the human liver has revealed that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. Reactive oxygen species (ROS) are involved in the aging process and result mainly from nonenzymatic processes in the liver.

Anantharaju, Abhinandana
Feller, Axel
Chedid, Antonio
Publication Title: 
The Biochemical Journal

NaCT (sodium-coupled citrate transporter) is an Na(+)-coupled citrate transporter identified recently in mammals that mediates the cellular uptake of citrate. It is expressed predominantly in the liver. NaCT is structurally and functionally related to the product of the Indy (I'm not dead yet) gene in Drosophila, the dysfunction of which leads to lifespan extension. Here, we show that NaCT mediates the utilization of extracellular citrate for fat synthesis in human liver cells, and that the process is stimulated by lithium.

Inoue, Katsuhisa
Zhuang, Lina
Maddox, Dennis M.
Smith, Sylvia B.
Ganapathy, Vadivel
Publication Title: 

XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA lesions and cytotoxic DNA interstrand crosslinks. Mild mutations in XPF cause the cancer-prone syndrome xeroderma pigmentosum. A patient presented with a severe XPF mutation leading to profound crosslink sensitivity and dramatic progeroid symptoms. It is not known how unrepaired DNA damage accelerates ageing or its relevance to natural ageing. Here we show a highly significant correlation between the liver transcriptome of old mice and a mouse model of this progeroid syndrome.

Niedernhofer, Laura J.
Garinis, George A.
Raams, Anja
Lalai, Astrid S.
Robinson, Andria Rasile
Appeldoorn, Esther
Odijk, Hanny
Oostendorp, Roos
Ahmad, Anwaar
van Leeuwen, Wibeke
Theil, Arjan F.
Vermeulen, Wim
van der Horst, Gijsbertus T. J.
Meinecke, Peter
Kleijer, Wim J.
Vijg, Jan
Jaspers, Nicolaas G. J.
Hoeijmakers, Jan H. J.
Publication Title: 
PLoS genetics

Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan. In contrast, mouse models for DNA repair-deficient progeroid syndromes age and die prematurely. To identify mechanisms that regulate mammalian longevity, we quantified the parallels between the genome-wide liver expression profiles of mice with those two extremes of lifespan. Contrary to expectation, we find significant, genome-wide expression associations between the progeroid and long-lived mice.

Schumacher, Bjˆrn
van der Pluijm, Ingrid
Moorhouse, Michael J.
Kosteas, Theodore
Robinson, Andria Rasile
Suh, Yousin
Breit, Timo M.
van Steeg, Harry
Niedernhofer, Laura J.
van Ijcken, Wilfred
Bartke, Andrzej
Spindler, Stephen R.
Hoeijmakers, Jan H. J.
van der Horst, Gijsbertus T. J.
Garinis, George A.
Publication Title: 
Biochimica Et Biophysica Acta

This review describes our current understanding of the "traffic lights" that regulate sulfur flow through the methionine bionetwork in liver, which supplies two major homeostatic systems governing cellular methylation and antioxidant potential. Theoretical concepts derived from mathematical modeling of this metabolic nexus provide insights into the properties of this system, some of which seem to be paradoxical at first glance. Cellular needs supported by this network are met by use of parallel metabolic tracks that are differentially controlled by intermediates in the pathway.

Martinov, M. V.
Vitvitsky, V. M.
Banerjee, R.
Ataullakhanov, F. I.
Publication Title: 
PloS One

BACKGROUND: Zinc deficiency due to poor nutrition or genetic mutations in zinc transporters is a global health problem and approaches to providing effective dietary zinc supplementation while avoiding potential toxic side effects are needed. METHODS/PRINCIPAL FINDINGS: Conditional knockout of the intestinal zinc transporter Zip4 (Slc39a4) in mice creates a model of the lethal human genetic disease acrodermatitis enteropathica (AE).

Geiser, Jim
De Lisle, Robert C.
Finkelstein, David
Adlard, Paul A.
Bush, Ashley I.
Andrews, Glen K.
Publication Title: 
Scientific Reports

The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed.

Villano, Gianmarco
Ruvoletto, Mariagrazia
Ceolotto, Giulio
Quarta, Santina
Calabrese, Fiorella
Turato, Cristian
Tono, Natascia
Biasiolo, Alessandra
Cattelan, Arianna
Merkel, Carlo
Avogaro, Angelo
Gatta, Angelo
Pontisso, Patrizia
Publication Title: 
Biochemical Society Transactions
Hales, C. N.
Desai, M.
Ozanne, S. E.
Crowther, N. J.
Publication Title: 
Biological Reviews of the Cambridge Philosophical Society

Fetal growth and development is dependent upon the nutritional, hormonal and metabolic environment provided by the mother. Any disturbance in this environment can modify early fetal development with possible long-term outcomes as demonstrated by extensive work on 'programming'. Growth restriction resulting from a deficit in tissue/organ cell number (as measured by tissue DNA content) is irrecoverable. However, when the cell size (or cell protein content) is reduced, the effects on growth may not be permanent.

Desai, M.
Hales, C. N.
Publication Title: 
The Journal of Nutrition, Health & Aging

Aging is an inevitable characteristic of biological processes in living organisms. For the last several years, investigators have proposed numerous mechanisms to explain the basic understanding of aging and its intervention and have provided many insights into the molecular bases and the biological events that contribute to the progressive decline in function observed during cellular aging.

Srivastava, V. K.
Miller, S. D.
Busbee, D. L.


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