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Aging-related liver degeneration is associated with increased bacterial endotoxin and lipopolysaccharide binding protein levels.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2020 Apr 01; Vol. 318 (4), pp. G736-G747. Date of Electronic Publication: 2020 Feb 24. - Publication Year :
- 2020
-
Abstract
- Aging is a risk factor in the development of many diseases, including liver-related diseases. The two aims of the present study were 1 ) to determine how aging affects liver health in mice in the absence of any interventions and 2 ) if degenerations observed in relation to blood endotoxin levels are critical in aging-associated liver degeneration. Endotoxin levels and markers of liver damage, mitochondrial dysfunction, insulin resistance, and apoptosis as well as the Toll-like receptor 4 (Tlr-4) signaling cascade were studied in liver tissue and blood, respectively, of 3- and 24-mo-old male C57BL/6J mice. In a second set of experiments, 3- to 4-mo-old and 14-mo-old female lipopolysaccharide-binding protein (LBP) <superscript>-/-</superscript> mice and littermates fed standard chow, markers of liver damage, insulin resistance, and mitochondrial dysfunction were assessed. Plasma activity of aspartate aminotransferase and histological signs of hepatic inflammation and fibrosis were significantly higher in old C57BL/6J mice than in young animals. The number of neutrophils, CD8α-positive cells, and mRNA expression of markers of apoptosis were also significantly higher in livers of old C57BL/6J mice compared with young animals, being also associated with a significant induction of hepatic Tlr-4 and LBP expression as well as higher endotoxin levels in peripheral blood. Compared with age-matched littermates, LBP <superscript>-/-</superscript> mice display less signs of senescence in liver. Taken together, our data suggest that, despite being fed standard chow, old mice developed liver inflammation and beginning fibrosis and that bacterial endotoxin may play a critical role herein. NEW & NOTEWORTHY Old age in mice is associated with marked signs of liver degeneration, hepatic inflammation, and fibrosis. Aging-associated liver degeneration is associated with elevated bacterial endotoxin levels and an induction of lipopolysaccharide-binding protein (LBP) and Toll-like receptor 4-dependent signaling cascades in liver tissue. Furthermore, in old aged LBP <superscript>-/-</superscript> mice, markers of senescence seem to be lessened, supporting the hypothesis that bacterial endotoxin levels might be critical in aging-associated decline of liver.
- Subjects :
- Acute-Phase Proteins genetics
Animals
Apoptosis
Biomarkers
Carrier Proteins genetics
Female
Gene Expression Regulation
Glucose metabolism
Inflammation pathology
Insulin Receptor Substrate Proteins genetics
Insulin Receptor Substrate Proteins metabolism
Liver metabolism
Malate Dehydrogenase genetics
Malate Dehydrogenase metabolism
Male
Membrane Glycoproteins genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
RNA, Messenger
Receptor, Insulin genetics
Receptor, Insulin metabolism
Toll-Like Receptor 4 genetics
Toll-Like Receptor 4 metabolism
Acute-Phase Proteins metabolism
Aging
Carrier Proteins metabolism
Endotoxins blood
Liver pathology
Liver Cirrhosis pathology
Membrane Glycoproteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1547
- Volume :
- 318
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 32090603
- Full Text :
- https://doi.org/10.1152/ajpgi.00345.2018