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

1982 ◽  
Vol 202 (1) ◽  
pp. 47-51 ◽  
Author(s):  
L Lavie ◽  
A Z Reznick ◽  
D Gershon

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.

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1789
Author(s):  
Dare E. George ◽  
Jetze J. Tepe

The proteasome system is a large and complex molecular machinery responsible for the degradation of misfolded, damaged, and redundant cellular proteins. When proteasome function is impaired, unwanted proteins accumulate, which can lead to several diseases including age-related and neurodegenerative diseases. Enhancing proteasome-mediated substrate degradation with small molecules may therefore be a valuable strategy for the treatment of various neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. In this review, we discuss the structure of proteasome and how proteasome’s proteolytic activity is associated with aging and various neurodegenerative diseases. We also summarize various classes of compounds that are capable of enhancing, directly or indirectly, proteasome-mediated protein degradation.


2015 ◽  
Vol 112 (33) ◽  
pp. 10515-10520 ◽  
Author(s):  
Yuji Takihara ◽  
Masaru Inatani ◽  
Kei Eto ◽  
Toshihiro Inoue ◽  
Alexander Kreymerman ◽  
...  

The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23–25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.


2021 ◽  
Vol 7 (21) ◽  
pp. eabe4601
Author(s):  
Sandro Da Mesquita ◽  
Jasmin Herz ◽  
Morgan Wall ◽  
Taitea Dykstra ◽  
Kalil Alves de Lima ◽  
...  

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases.


1980 ◽  
Vol 238 (1) ◽  
pp. E46-E52
Author(s):  
S. L. Augustine ◽  
R. W. Swick

The recovery of approximately 40% of the total liver protein during the first day after partial hepatectomy was shown to be due to the near cessation of protein breakdown rather than to an increase in protein synthesis. The decrease in degradation of total protein was less if rats were adrenalectomized or protein-depleted prior to partial hepatectomy. The effect of these treatments originally suggested that changes in free amino acid levels in liver might be related to the rate of protein degradation. However, no correlation was found between levels of total free amino acids and rates of breakdown. Measurements of individual amino acids during liver regeneration suggested that levels of free methionine and phenylalanine, amino acids that have been found to lower rates of protein degradation in vitro, are not correlated with rates of breakdown in vivo. The difference between the fractional rate of ornithine aminotransferase degradation (0.68/day and 0.28/day in sham-hepatectomized and partially hepatectomized rats, respectively) was sufficient to account for the higher level of this protein 3 days after surgery in the latter group.


2008 ◽  
Vol 294 (4) ◽  
pp. H1562-H1570 ◽  
Author(s):  
Hélène Bulckaen ◽  
Gaétan Prévost ◽  
Eric Boulanger ◽  
Géraldine Robitaille ◽  
Valérie Roquet ◽  
...  

The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Age-related endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2′-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60- and 84-wk-old mice ( P < 0.05); 68-wk-old mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 ± 4 vs. 66.3 ± 5%; P < 0.05). Aspirin treatment decreased 8-OHdG levels ( P < 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress.


1990 ◽  
Vol 237 (3-4) ◽  
pp. 131-146 ◽  
Author(s):  
Karen Swisshelm ◽  
Christine M. Disteche ◽  
Joanne Thorvaldsen ◽  
Andrew Nelson ◽  
Darrell Salk

1999 ◽  
Vol 13 (7) ◽  
pp. 599-603 ◽  
Author(s):  
Robert H Riddell

In the paediatric population, the associations ofHelicobacter pyloriwith gastritis, gastric ulcer, duodenitis and duodenal ulcer, and with duodenal gastric surface metaplasia and disorders of the D cell-G cell axis resulting in hypergastrinemia, are well established and in many ways resemble their counterparts in adults. Eradication ofH pyloriinvariably results in the reversal of these diseases with time. There are also suggestions that gastric surface metaplasia is more extensive in children withH pylori, and may be the site of duodenalH pyloriinfection and associated duodenal erosions or ulcers. There is no consensus as to whetherH pyloriin children is more or less severe than in adults. In one paediatric cohort,H pyloriwas associated with increased intensity of inflammation, while other studies suggest that acute inflammation may be less intense in children overall but that chronic inflammation may be increased in intensity, including lymphoid hyperplasia, which in turn may correlate with endoscopic nodularity. Lymphoid hyperplasia and nodular gastritis appear to be more frequent in children than in adults and usually regress followingH pylorieradication. However, in children, other diseases or morphological abnormalities, including some loss of glands (atrophy), occasionally intestinal metaplasia, lymphoproliferative diseases including low grade mucosal-associated lymphoid tissue lymphoma, lymphocytic gastritis and hypertrophic gastritis/Menetrier’s disease, are much less frequently associated withH pylorithan in adults. Other associations are rarely seen in children, primarily because the time required for these to develop takes the individual to adulthood; for example, while intestinal metaplasia occurs in the pediatric population, the complications of adenoma/dysplasia and carcinoma are rare. In adults, inflammatory and hyperplastic polyps, atrophic gastritis and pernicious anemia, and in some patients granulomas (granulomatous gastritis), may also be associated withH pyloriinfection. Greater awareness of the spectrum of diseases associated withH pylorimay well lead to their increased recognition in the paediatric population. Some diseases, particularly Crohn’s disease, but also human immunodeficiency virus infection, have a negative association withH pylorithat appears not to be simply a result of the excess antibiotic therapy that these patients receive. These variations in association and reactions toH pylori, some of which are age-related, may allow the different host responses toH pylorithat occur in humans to be examined.


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