Aging Liver

Anantharaju, Abhinandana; Feller, Axel G.; Chedid, Antonio

doi:10.1159/000065506

Cited by 167 publications

(51 citation statements)

References 84 publications

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“…We detected lipofuscin in 41 of 68 cadaveric livers (60.2%). Although the data are in accordance with the notion that lipofuscin expression is associated with the liver of old age (Anantharaju et al, 2002;Schmucker, 2005), its absence (in the reaming 40% of the aged cadaveric livers) suggests that lipofuscin is not sine qua non of the aging liver. Given the cadaver age range 56-100, the question was raised which liver pathologic lesions were likely in the very elderly.…”

Section: Resultssupporting

confidence: 86%

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Hepatic Steatosis, Fibrosis, and Cancer in Elderly Cadavers

Mak

Kwong

Chu

et al. 2011

The Anatomical Record

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The incidence of hepatic steatosis, fibrosis, and cancer in the elderly population remains unknown. Human cadavers used in anatomy teaching, which come largely from older adults, may provide liver tissue for examining their pathologies. Livers were obtained from 68 cadavers (mean age 82.1 ± 10.4 years) with diverse causes of death in the Anatomy course at Mount Sinai School of Medicine. Paraffin sections were stained with hematoxylin and eosin and Sirius red and evaluated for steatosis, fibrosis, cancer, and lipofuscin. Tissue preservation was graded as good in 38.2% of the embalmed livers, fair in 36.7%, and poor in 25.0%. Steatosis was observed in 35.3% of the livers, central vein fibrosis in 49.2%, perisinusoidal fibrosis in 63.2%, portal tract (PT) fibrosis in 47.0%, septa formation in 44.1%, bridging fibrosis in 30.8%, and cirrhosis in 4.4%. One hepatocellular carcinoma (HCC) and six metastatic tumors were detected. Lobular inflammation occurred in 20.8% of the livers and PT inflammation in 38.8%. Nine livers showed minimal change. Lipofuscin was detected in 60.2% of the livers. Steatosis, fibrosis, and cancer are highly prevalent in elderly cadavers with diverse causes of death. The prevalence of steatosis and fibrosis is consistent with the data in patients with specific liver diseases. Steatosis alongside fibrosis can accelerate the progression of fibrosis to cirrhosis and ultimately HCC. Though not indicated as the primary cause of death, the liver injury may have compromised hepatic functions and enhanced disease susceptibility, thereby exacerbating the health conditions in this elderly population. Anat Rec, 2012. © 2011 Wiley Periodicals, Inc.

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Section: Resultssupporting

confidence: 86%

“…The question was raised whether elderly cadavers express lipofuscin, an aging pigment associated with the liver of older people (Tygstrup et al, 1965;Anantharaju et al, 2002;Schmucker, 2005). Accordingly, we looked for lipofuscin in H&E section, which appears as yellowbrown granules in the hepatocytes.…”

Section: Lipofuscin Detectionmentioning

confidence: 99%

Hepatic Steatosis, Fibrosis, and Cancer in Elderly Cadavers

Mak

Kwong

Chu

et al. 2011

The Anatomical Record

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“…As an oxidative stress-inducible gene, basal increases in gadd153 expression are consistent with the idea that aging is associated with elevated levels of ROS and chronic oxidative stress (4,50). However, it is also possible that changes in gadd153 contribute to elevations in ROS, as we have shown that ectopic expression of Gadd153 in rat fibroblasts leads to increased levels of ROS (41).…”

Section: Ros Contribute To Increasing Gadd153 Levels By Egf Treatmentsupporting

confidence: 83%

Expression of the Pro-apoptotic Genegadd153/chop Is Elevated in Liver with Aging and Sensitizes Cells to Oxidant Injury

Ikeyama

Wang

et al. 2003

Journal of Biological Chemistry

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Aging is generally accompanied by reduced tolerance to oxidative stress and altered responsiveness to proliferative signals. We have shown that hepatocytes derived from aged rats (24 -26 months) exhibit greater sensitivity to H 2 O 2 treatment and reduced proliferation following epidermal growth factor (EGF) treatment than cells of young adult rats (5-6 months). Here we examined the effects of aging and calorie restriction (CR) on expression of the oxidative stress-inducible and pro-apoptotic gene gadd153 (chop) in these hepatocytes, and we investigated its influence on sensitivity to oxidants. We show that aging was associated with elevated expression of gadd153, both basally and in response to H 2 O 2 treatment. CR, which attenuates age-associated declines in stress tolerance, prevented the age-related increase in gadd153 expression. EGF treatment also resulted in gadd153 induction in old cells. This effect was absent in young cells and in old cells of CR rats. gadd153 induction by EGF was reactive oxygen species-dependent and correlated with heightened sensitivity to subsequent H 2 O 2 treatment, suggesting that elevated Gadd153 contributes to the greater sensitivity of EGF-pretreated old cells to oxidative stress. Additional support for this hypothesis was provided by experiments with Rat1 fibroblasts in which conditional expression of Gadd153 conferred increased sensitivity to H 2 O 2 . We propose a model whereby the diminished ability of old hepatocytes to overcome an EGF-triggered reactive oxygen species load leads to induction of the proapoptotic gene gadd153, which, in turn, sensitizes the cells to oxidant injury. Our findings point to gadd153 expression levels as an important factor in liver aging.

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“…This is probably due to a reduction in liver mass and blood flow [52]. As a result, the bioavailability of drugs undergoing extensive first-pass metabolism such as propranolol and labetalol can be significantly increased [53][54][55].…”

Section: First-pass Metabolism and Bioavailabilitymentioning

confidence: 99%

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Mangoni

Jackson

2003

Brit J Clinical Pharma

1,385

911

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Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiolog ical stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.

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Aging Liver

Cited by 167 publications

References 84 publications

Hepatic Steatosis, Fibrosis, and Cancer in Elderly Cadavers

Hepatic Steatosis, Fibrosis, and Cancer in Elderly Cadavers

Expression of the Pro-apoptotic Genegadd153/chop Is Elevated in Liver with Aging and Sensitizes Cells to Oxidant Injury

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

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