Changes in Brain Protein Synthesis during the Life Span of Male Fischer Rats

Ekstrom, R. David; Liu, Daniel S H; Richardson, Arlan

doi:10.1159/000212405

Cited by 59 publications

(14 citation statements)

References 17 publications

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“…They found that each tissue has a distinct pattern of incorporation of [14C]leucine into protein as a function of age. The decrease with age in protein synthesis of rat (Breuer & Florini, 1965) and mouse (Srivastava, 1969) skeletal muscle, of rat brain (Murthy & Rappoport, 1965;Ekstrom, Liu & Richardson, 1980), and the increase in rat liver (Murthy, 1966) in in vitro systems agree with the in vivo results of Kanungo et al (1970). In contrast, Mainwaring (1969) observed a decline in the in vitro incorporation of [Wlphenylalanine into the liver of old mice, and a decline in the in vivo rate of liver protein synthesis has been observed in old Sprague-Dawley rats .…”

Section: Rationale For the Study Of Protein Metabolism During Agingsupporting

confidence: 74%

Protein Synthesis and Degradation During Aging and Senescence

Makrides

1983

Biological Reviews

171

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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...

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Section: Rationale For the Study Of Protein Metabolism During Agingsupporting

confidence: 74%

Protein Synthesis and Degradation During Aging and Senescence

Makrides

1983

Biological Reviews

171

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“…The other mechanism is decreasing content of the enzyme molecules, which manifests in late senescence (Table I). It is known that the rates of protein synthesis and turnover in several tissues, such as brain, liver, and thymus, decrease in aged animals (30)(31)(32). Therefore, we speculate that the Na + , K + -ATPase activity of SPM decreases by two mechanisms: an altered lipid microenvironment, which starts from the early stages of senescence; and a diminished enzyme content in the late stages.…”

Section: Discussionmentioning

confidence: 84%

Age-Related Changes in [3H]Ouabain Binding to Synaptic Plasma Membranes Isolated from Mouse Brains1

Tanaka

Ando²

1992

The Journal of Biochemistry

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Age-related changes in ouabain binding to synaptic plasma membranes isolated from cerebral cortices of C57BL/6 mice were investigated to examine whether the density of Na+, K(+)-ATPase decreases with advancing age. Specific binding of [3H]ouabain did not change until around 20 months of age, but a 22% decrease in binding was found in the late senescent stage (29 months). Scatchard analysis of the binding revealed that the maximum number of binding sites (Bmax) was lower in aged mice, while the binding affinity (Kd) for ouabain receptor remained unchanged with aging. These results indicate that the density of Na+,K(+)-ATPase enzyme sites in the plasma membranes of brain synapses decreases in aged mice. Since the activity of Na+,K(+)-ATPase has been found to start declining at a much earlier stage [Tanaka, Y. & Ando, S. (1990) Brain Res. 506, 46-52; Ando, S. & Tanaka, Y. (1990) Gerontology 36, 10-14] than that at which the decrease of Bmax is manifested, at least two mechanisms may underlie the age-related decrease of the enzyme activity. We speculate that the lipid microenvironment which regulates the enzyme activity starts to change at the early stage of senescence, followed by the decrease in the enzyme content in the later stage, that is, both changes cooperatively diminish the Na+,K(+)-ATPase activity in senescence.

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“…Prior to this time, the experimental methods did not consider specific activity of the precursor pool (reviewed by Richardson and Birchenall-Sparks, 1983), which resulted in highly variable outcomes across studies. Using improved methodology, several groups found that levels of brain protein synthesis increase during development in the rodent, reaching maximum levels sometime during the first 6 months of age, and then decline thereafter (Dwyer et al, 1980; Ekstrom et al, 1980; Fando et al, 1980; Ingvar et al, 1985; Smith et al, 1995; but see Filion and Laughrea, 1985; reviewed by Richardson, 1981; Richardson and Birchenall-Sparks, 1983; Richardson et al, 1983). A similar pattern was observed in the white leghorn chicken (Yang et al, 1977).…”

Section: Transcription and Translation In The Aging Brainmentioning

confidence: 99%

“…A similar pattern was observed in the white leghorn chicken (Yang et al, 1977). There is some disagreement pertaining to the exact time course of the decline, with some finding a greater rate of decline in translation during adulthood (Ekstrom et al, 1980; Fando et al, 1980; Ingvar et al, 1985; Smith et al, 1995), and others finding the greatest rate of decline during senescence (Dwyer et al, 1980). Similarly, although protein synthesis decline has been observed in many other types of tissues and cells (e.g., liver, kidney, muscle), the time courses and rates of decline vary (reviewed by Webster, 1985).…”

Section: Transcription and Translation In The Aging Brainmentioning

confidence: 99%

Neural protein synthesis during aging: effects on plasticity and memory

Schimanski

Barnes

2010

Fronti.Ag.Neurosci.

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During aging, many experience a decline in cognitive function that includes memory loss. The encoding of long-term memories depends on new protein synthesis, and this is also reduced during aging. Thus, it is possible that changes in the regulation of protein synthesis contribute to the memory impairments observed in older animals. Several lines of evidence support this hypothesis. For instance, protein synthesis is required for a longer period following learning to establish long-term memory in aged rodents. Also, under some conditions, synaptic activity or pharmacological activation can induce de novo protein synthesis and lasting changes in synaptic transmission in aged, but not young, rodents; the opposite results can be observed in other conditions. These changes in plasticity likely play a role in manifesting the altered place field properties observed in awake and behaving aged rats. The collective evidence suggests a link between memory loss and the regulation of protein synthesis in senescence. In fact, pharmaceuticals that target the signaling pathways required for induction of protein synthesis have improved memory, synaptic plasticity, and place cell properties in aged animals. We suggest that a better understanding of the mechanisms that lead to different protein expression patterns in the neural circuits that change as a function of age will enable the development of more effective therapeutic treatments for memory loss.

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Changes in Brain Protein Synthesis during the Life Span of Male Fischer Rats

Cited by 59 publications

References 17 publications

Protein Synthesis and Degradation During Aging and Senescence

Protein Synthesis and Degradation During Aging and Senescence

Age-Related Changes in [3H]Ouabain Binding to Synaptic Plasma Membranes Isolated from Mouse Brains1

Neural protein synthesis during aging: effects on plasticity and memory

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