Age-Related Changes in the Hepatic Endoplasmic Reticulum: A Quantitative Analysis

Schumucker, Douglas L.; Mooney, Jill S.; Jones, Albert L.

doi:10.1126/science.887935

Cited by 57 publications

(11 citation statements)

References 25 publications

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“…1,2,23 These results are consistent with past studies, all of which conclude that there are few gross structural changes in the liver with age. 1,2,23 Previous electron-microscopic studies have not reported specific investigations of sinusoidal structures in the intact aged liver 14,[24][25][26][27] ; however, our assessment by electron microscopy and immunohistochemistry revealed significant age-related changes within the sinusoidal endothelium and space of Disse. Scanning electron microscopy revealed a significant reduction in the porosity of the aged sinusoidal endothelium.…”

Section: Discussioncontrasting

confidence: 46%

“…12 In marked contrast to cirrhosis, the effect of aging on the ultrastructure of the sinusoidal endothelium and space of Disse has not been well characterized. Most structural studies have reported changes of hepatocytes, including increased hepatocyte volume, polyploidy, lysosomes, and lipofuscin, 1 or changes in mitochondria 13 and endoplasmic reticulum 14 ; however, all studies have failed to detect any evidence of classical pathologic processes.…”

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confidence: 99%

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Pseudocapillarization and associated energy limitation in the aged rat liver

2001

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Age-related impairment of drug metabolism by the liver is consistent with hepatocyte hypoxia, suggestive of the development of a diffusional barrier to oxygen supply. Because the effects of aging on the diffusional pathway (sinusoidal endothelium and space of Disse) have not been described, we performed comparative studies on the livers of Fischer F344 rats aged 4 to 7, 12 to 15, and 24 to 27 months. Lightmicroscopic examination revealed no evidence of fibrosis, cirrhosis, or other specific pathology. In contrast, scanning and transmission electron-microscopic examination revealed that aging is associated with pseudocapillarization of the sinusoidal endothelium, indicated by defenestration with reduced porosity, thickening of the endothelium, infrequent development of basal lamina, and only minor collagen deposits in the space of Disse. Furthermore, immunohistochemistry studies showed strong expression of collagen IV, moderate expression of factor VIII-related antigen, and weak expression of collagen I along the sinusoids of livers from old rats (P < .0001). In vitro 31 P magnetic resonance spectroscopy analysis showed that aging is associated with changes in high-energy phosphate and other metabolites, consistent with hepatocyte hypoxia. Aging in the liver is associated with changes in the sinusoidal endothelium and space of Disse that may restrict the availability of oxygen and other substrates. (HEPATOLOGY 2001;33:537-543.)The effect of aging in the liver is often considered to be of a lesser degree than in other organs. [1][2][3][4] The major recognized changes in the aging liver include reduction in liver mass and hepatic blood flow 1,4,5 ; however, it has been concluded that there are few other significant structural or biochemical changes in the liver. 1,2 On the other hand, even subtle agerelated changes may have profound consequences for the rest of the body. For example, any age-related impairment in hepatic drug and xenobiotic detoxification could partly explain the susceptibility of elderly persons to adverse drug reactions or illnesses with toxic etiology. 5 In vivo, the hepatic clearance of many drugs is reduced in elderly persons. Traditional theories have attempted to attribute this to age-related reduction of liver mass and blood flow. 6 However, in a recent review, 5 we noted that there appears to be selective reduction of the clearance of drugs that undergo phase I metabolism, associated with preservation of the clearance of drugs that undergo phase II metabolism. Even more puzzling, the in vitro activities of phase I enzymes are maintained into old age. 7 Because these paradoxes cannot be attributed to changes in blood flow and liver mass alone, we suggested an explanation based on oxygen supply, as the activities of phase I enzymes are highly oxygen-dependent because they require oxygen as a substrate. 8 We hypothesized the development of a barrier to oxygen diffusion, leading to functional intracellular hypoxia in the hepatocytes of the aging liver. This provides a plausible mechanism for i...

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Section: Discussioncontrasting

confidence: 46%

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confidence: 99%

Pseudocapillarization and associated energy limitation in the aged rat liver

2001

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“…Information concerning the effects of aging on other hepatocellular membrane compartments, e.g., the smooth-surfaced endoplasmic reticulum (SER), is conflicting. Our own stereological analyses demonstrated a significant loss of SER from rat hepatocytes in lobular zones 1 and 3 between maturity and senescence (21,41). This observation correlates well with a concomitant decline in the yield of liver microsomal protein from similarly aged rats of the same strain (42).…”

Section: Liver Morphologysupporting

confidence: 53%

“…Asterisks (*), bile canaliculi; arrows, rough surfaced endoplasmic reticulum; S, sinusoidal surface or space of Disse. 7,000-9,500X tant shifts in the protein synthesizing capacity of the rat liver during aging (21,(37)(38)(39)(40)(41). Information concerning the effects of aging on other hepatocellular membrane compartments, e.g., the smooth-surfaced endoplasmic reticulum (SER), is conflicting.…”

Section: Liver Morphologymentioning

confidence: 99%

Aging and the Liver: An Update

Schmucker

1998

The Journals of Gerontology Series A: Biological Sciences and M

164

104

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“…Furthermore, since MAPS directly affect monomer-polymer equilibrium by promoting tubulin assembly in vitro (14) and possibly in vivo ( 19), the loss of MAPS-tubulin affinity may also reduce the relative amount of tubulin assembled in old animals. Since we have shown that the in situ concentration of hepatocyte smooth-surfaced endoplasmic reticulum and the yield of hepatic microsomes decline substantially during aging in rats, we do not suspect that the age-related changes in polymerized tubulin and MAPS reflect concomitant differences in the binding of these moieties to membranes during isolation (20,21). Since liver cells from old rats contain less membrane than those from young animals, we suggest that less.…”

Section: Discussionmentioning

confidence: 84%

Surgical Influence on Murine Immunity and Tumor Growth: Relationship of Body Temperature and Hormones with Splenocytes

Ratajczak

Lange

Sothern

et al. 1992

Experimental Biology and Medicine

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Adrenalectomy predisposed the C3HeB/FeJ Mouse to tumor from a low dose of tumor cells, derived from a C3H spontaneous mammary adenocarcinoma. Sham surgery had a similar effect. In contrast, ovariectomized females, intact females, and male mice did not allow the low dose of cells to develop into a tumor. In order to better understand the role of hormones on the immune system controlling tumor growth, normal C3HeB/FeJ mice were studied for the effect of corticosterone or estradiol on splenic lymphocyte surface antigen expression. Adrenalectomy and ovariectomy caused a decrease in the percentage of all T cell subclasses and an increase in absolute numbers of immunoglobulin-bearing cells. Reconstitution of ovariectomized mice with estradiol did not significantly alter lymphocyte cell surface antigen expression. In contrast, injection of corticosterone into adrenalectomized mice brought these values to normal. Further study on normal mice placed on a 12:12-hr light:dark schedule showed that the hours after lights on (HALO) had a significant effect (analysis of variance) on body temperature, percentage of splenic B cells, T pan, T helper and T suppressor cells, and absolute numbers of T pan cells. Brain dehydroepiandrosterone sulfate correlated positively with T pan lymphocytes, but showed no significant effect on HALO. In contrast, body temperature showed a strong circadian rhythm (P less than 0.001). In addition, the presentation of estrus was circadian rhythmic (P = 0.003) with 58% of mice in estrus at 16 HALO and only 8% at 4 HALO. Multiple regression analysis revealed body temperature was strongly associated with absolute numbers of splenic T lymphocytes and their subsets, as well as percentage of B lymphocytes, Thy 1.2-, and Lyt-2-bearing cells. Similarly, HALO and estrous cycle stage were associated with percentage of T helper cells. The data showed that body temperature and hormones were associated with the cell surface antigens on lymphocytes and suggest that they affect lymphocyte function.

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Age-Related Changes in the Hepatic Endoplasmic Reticulum: A Quantitative Analysis

Cited by 57 publications

References 25 publications

Pseudocapillarization and associated energy limitation in the aged rat liver

Pseudocapillarization and associated energy limitation in the aged rat liver

Aging and the Liver: An Update

Surgical Influence on Murine Immunity and Tumor Growth: Relationship of Body Temperature and Hormones with Splenocytes

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