Age-associated changes in activities of rat hepatocytes. I. Protein synthesis

Viskup, Robert W.; Baker, Mary T.; Holbrook, Joan P.; Penniall, Ralph

doi:10.1080/03610737908257223

Cited by 16 publications

(6 citation statements)

References 13 publications

(8 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The partial recovery of cell responses may be due to incomplete electroporation efficiency combined with the transient expression or to age-related decrements in general cell functioning such as protein synthesis (52)(53)(54)(55), which is involved in cell motility (15,56) and mitogenesis (35). The ramification of these findings for wound healing are obvious.…”

Section: Discussionmentioning

confidence: 99%

Aging Fibroblasts Present Reduced Epidermal Growth Factor (EGF) Responsiveness Due to Preferential Loss of EGF Receptors

Shiraha¹,

Gupta²,

Drabik³

et al. 2000

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

Wound healing is compromised in aging adults in part due to decreased responsiveness of fibroblasts to extracellular signals. However, the cellular mechanisms underlying this phenomenon are not known. Aged dermal fibroblasts with reduced remaining replicative capacities demonstrated decreased epidermal growth factor (EGF)-induced cell migrative and cell proliferative capacities, as reported previously. Thus, as cells approach senescence, programmed in vivo or in vitro, EGF responsiveness is preferentially lost. To define the rate-limiting signaling event, we found that the activity of two different EGF receptor (EGFR)-signaling pathways to cell migration (phospholipase-C ␥) and/or mitogenesis (extracellular signal/regulated-mitogen-activated kinases) were decreased in near senescent cells despite unchanged levels of effector molecules. Aged cells presented decreased levels of EGFR, although insulin receptor and transferrin receptor levels were relatively unchanged. EGFR mRNA levels and production of new transcripts decreased during aging, suggesting that this preferential loss of EGFR was due to diminished production, which more than counteracts the reduced ligand-induced receptor loss. Since these data suggested that the decrement in EGF was rate-limiting, higher levels of EGFR were established in near senescent cells by electroporation of EGFR cDNA. These cells presented higher levels of EGFR and recovered their EGF-induced migration and proliferation responsiveness. Thus, the defect in EGF responsiveness of aged dermal fibroblasts is secondary to reduced EGFR message transcription. Our experimental model suggests that EGFR gene delivery might be an effective future therapy for compromised wound healing.

show abstract

Section: Discussionmentioning

confidence: 99%

Aging Fibroblasts Present Reduced Epidermal Growth Factor (EGF) Responsiveness Due to Preferential Loss of EGF Receptors

Shiraha¹,

Gupta²,

Drabik³

et al. 2000

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

show abstract

“…Much research over the past two decades has focused on the relationship between aging and protein synthesis in the liver. [9][10][11][12] The data generally indicate that total protein synthetic activity in the liver declines with increasing age. Ward 14 studied the age-related changes in the liver protein synthesis of Fischer 344 rats by measuring the valine incorporation rate in the perfused liver.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, serum albumin concentrations have been reported to decline in the elderly, suggesting a decline in hepatic protein synthesis with age, 9,10 which many investigators have confirmed experimentally in rodents. 11,12 We investigated the impact of these age-related alterations in liver grafts on post-transplantation liver functions and the growth of young inbred Fisher 344 rat recipients.…”

Section: Introductionmentioning

confidence: 99%

Impact of Donor Age on the Growth of Young Recipient Rats After Liver Transplantation

et al. 2006

View full text Add to dashboard Cite

show abstract

“…In contrast, Viskup et al (1979) reported that a protein component of ca. 20000 Daltons remained unlabelled by hepatocytes from aged male rats of the Sprague-Dawley strain.…”

Section: (B) Isolated Hepatocytes In Culturementioning

confidence: 94%

Protein Synthesis and Degradation During Aging and Senescence

Makrides

1983

Biological Reviews

171

View full text Add to dashboard Cite

Summary 1. The published results on protein synthesis during aging are contradictory. Possible sources of error and variability include: an insufficient number of different animal ages used; use of whole organs that are cytologically highly heterogeneous; different animal strains; neglecting to measure the specific activity of the precursor pool for protein synthesis; and inadequate methodology for measurement of in vivo rates of protein synthesis. 2. In general, protein synthesis rates in mammals have been reported to decline 4–70% with age. In insects and other organisms, greater losses (60–90%) have been observed. 3. Limited evidence indicates that in some systems a decline in the rate of protein synthesis may be due to alterations (as yet of unknown nature) in the initiation components of the protein synthetic apparatus. Futhermore, some studies suggest that in some organisms aging affects the expression of specific parts of the genome. 4. The significance of results on protein metabolism obtained from some studies with nematodes is at present unknown, owing to problems associated with age‐synchronization methods. Also, the in vitro fibroblast system for the study of human cellular aging has not been met with universal acceptance; it is generally believed that this system has not yet been established as a valid analogy to mammalian aging in vivo. 5. Failure to detect defective enzymes in many old organisms indicates at least that not all proteins are altered during aging. The complete thermal stability of purified enzymes from old organisms suggests that the observed thermolability of the same enzymes in crude cell extracts is not an intrinsic property of those enzymes. Post‐translational modifications (partial denaturation) may constitute the primary mechanism for the production of altered cell polypeptides during aging. 6. The available evidence does not support the concept of an age‐dependent decline in translational accuracy. The future purification to absolute homogeneity of an altered enzyme and its ‘young’ (unaltered) counterpart, and their sequencing, should resolve the question of translational errors. 7. Some degree of age‐related ribosome loss appears to occur in fixed postmitotic cells. In general, the published polyribosomal profiles may represent artefacts due to insufficiently suppressed ribonuclease activity during extraction. 8. The published studies on protein degradation during aging are also contradictory. Some investigators have neglected the possibility of reutilization of labelled amino acid. It is possible that some of the observed age‐related alterations in protein degradation rates are due to altered endocrine status of the animals used, rather than to defects in the protein degradative pathways. The studies utilizing cell culture systems are also contradictory, probably due to different experimental designs. 9. Limited evidence suggests that protein degradation may slow down with age in mammals and nematodes. An inefficient protein degradation system in old organisms could provide a...

show abstract

Age-associated changes in activities of rat hepatocytes. I. Protein synthesis

Cited by 16 publications

References 13 publications

Aging Fibroblasts Present Reduced Epidermal Growth Factor (EGF) Responsiveness Due to Preferential Loss of EGF Receptors

Aging Fibroblasts Present Reduced Epidermal Growth Factor (EGF) Responsiveness Due to Preferential Loss of EGF Receptors

Impact of Donor Age on the Growth of Young Recipient Rats After Liver Transplantation

Protein Synthesis and Degradation During Aging and Senescence

Contact Info

Product

Resources

About