The Isolated Hepatocyte: A Cellular Model for Aging Studies

Knook, D.L.

doi:10.3181/00379727-165-40954

Cited by 11 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An alternative proposal is that these modified proteins are more prone to degradation in autophagic vacuoles which involve lysosomal proteinases. Lysosomal cathepsin activity has been shown to increase with age in hepatocytes (Knook, 1980). These explanations should be considered speculative as long as the understanding of the nature of the protein-degradation pathways in cells remain obscure.…”

Section: Discussionmentioning

confidence: 99%

Decreased protein and puromycinyl-peptide degradation in livers of senescent mice

Lavie¹,

Reznick²,

Gershon³

1982

Biochemical Journal

103

View full text Add to dashboard Cite

Liver protein-degradation rates were determined in young and old C57B1 mice by the method of Swick & Ip [(1974) J. Biol. Chem. 249, 6836-6841]. The results indicated a marked age-related increase in the half-lives of short-lived proteins in the nuclear, mitochondrial, lysosomal and 100000 g-supernatant cellular fractions and in total trichloroacetic acid-precipitable proteins. The efficiency of the degradation system in removing aberrant proteins from livers of young and old mice was tested. The time required for 50% disappearance of puromycinyl-peptides changed from about 20 min in 6-month-old mice to approx. 150 min in 24-month-old animals. These findings suggest that in old animals the proteolytic activity involved in degradation of aberrant proteins, and presumably of "native proteins, is markedly defective.

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased protein and puromycinyl-peptide degradation in livers of senescent mice

Lavie¹,

Reznick²,

Gershon³

1982

Biochemical Journal

103

View full text Add to dashboard Cite

show abstract

“…The change in the rate of lated hepatocyte is an excellent model for aging studies. 9 This gluconeogenesis was not accompanied by changes in is especially useful when attempting to study aging at the any of the following parameters: phosphoenolpyruvate cellular level, using whole cells. carboxykinase or pyruvate carboxylase activities or miTo our knowledge, no attempts have been made to correlate tochondrial ATP/ADP or cytosolic NADH/NAD / ratios.…”

mentioning

confidence: 99%

Aging of the liver: Age-associated mitochondrial damage in intact hepatocytes

et al. 1996

View full text Add to dashboard Cite

activated species.3 It is well known that fixed, postmitotic Mitochondrial damage may be a major cause of cellucells accumulate different age pigments, especially lipofuscin. lar aging. So far, this hypothesis had only been tested A considerable amount of this pigment may derive from inusing isolated mitochondria. The aim of this study was jured mitochondria. 4 This led us to propose a hypothesis 5 of to investigate the involvement of mitochondria in aging cell aging, according to which senescence is a by-product of using whole liver cells and not isolated mitochondria oxy-radical attack to the mitochondrial genome. only. Using flow cytometry, we found that age is associRecently, several studies have shown changes in mitochonated with a decrease in mitochondrial membrane potendria on aging. Age-related changes in mitochondrial respiratial (30%), an increase in mitochondrial size, and an intory function and in mitochondrial transport systems have crease in mitochondrial peroxide generation (23%).been reported. [6][7][8] All these changes were found in experiments Intracellular peroxide levels were also increased. The using isolated mitochondria. However, these effects could be number of mitochondria per cell and inner mitochoncaused by altered susceptibility of old mitochondria to the drial membrane mass did not change. Gluconeogenesis stress caused by the isolation procedure. Moreover, because from glycerol or fructose (mitochondrial-independent) intact cells were not used, the mitochondrial-cytosolic interdid not change with age, whereas it did from lactate actions were also ignored. This may lead to errors. The iso-(mitochondrial-dependent). The change in the rate of lated hepatocyte is an excellent model for aging studies. 9 This gluconeogenesis was not accompanied by changes in is especially useful when attempting to study aging at the any of the following parameters: phosphoenolpyruvate cellular level, using whole cells. carboxykinase or pyruvate carboxylase activities or miTo our knowledge, no attempts have been made to correlate tochondrial ATP/ADP or cytosolic NADH/NAD / ratios. age-associated changes in physiological functions of intact This was caused by a decreased rate of malate export cells with specific biochemical or molecular changes in mito-(to 20% of the controls) from mitochondria. The impairchondria. The aim of this study was to test whether mitochonment of the mitochondrial malate transporter is postdrial performance is impaired with aging, using intact liver transcriptional because its expression in Xenopus oocells. To this end, we have measured the rate of biochemical cytes using polyadenylated RNA from livers of young or pathways, gluconeogenesis, and ketogenesis, which critically old animals did not change. Ketogenesis from oleate also depend on mitochondrial function. In addition, we have used fell in hepatocytes from old rats. Our results show, for flow cytometry, which allows a noninvasive analysis of indithe first time in intact cells, a correlation between agevidual cells, to study ...

show abstract

The Ageing Process: Epidemiology, Theories and Model Systems

Knook

1989

Clinical Chemistry

View full text Add to dashboard Cite

The Isolated Hepatocyte: A Cellular Model for Aging Studies

Cited by 11 publications

References 13 publications

Decreased protein and puromycinyl-peptide degradation in livers of senescent mice

Decreased protein and puromycinyl-peptide degradation in livers of senescent mice

Aging of the liver: Age-associated mitochondrial damage in intact hepatocytes

The Ageing Process: Epidemiology, Theories and Model Systems

Contact Info

Product

Resources

About