scholarly journals Induction of G1 checkpoint in the gastric mucosa of aged rats

1999 ◽  
Vol 277 (5) ◽  
pp. G929-G934 ◽  
Author(s):  
Zhi-Qiang Xiao ◽  
Yingjie Yu ◽  
Ahmed Khan ◽  
Richard Jaszewski ◽  
Murray N. Ehrinpreis ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Proliferative Activity ◽  
Protein A ◽  
S Phase ◽  
Aged Rats ◽  
Fischer 344 Rats ◽  
Protein Levels ◽  
Fischer 344 ◽  
Age Related ◽  
P53 Status

Although in Fischer 344 rats aging is found to be associated with increased gastric mucosal proliferative activity, little is known about specific changes in the regulatory mechanisms of this process. To determine whether changes in cell cycling events could partly contribute to the age-related rise in gastric mucosal proliferative activity, the present investigation examines changes in cyclin-dependent kinase (Cdk2) activity and the regulation of this process in the gastric mucosa of Fischer 344 rats aged 4 (young), 13 (middle aged), and 24 (old) mo. We observed that aging is associated with a progressive rise in activity and protein levels of Cdk2 in the gastric mucosa. This is also found to be accompanied by a concomitant increase in cyclin E but not cyclin D1 levels. On the other hand, the levels of p21Waf1/Cip1 (total as well as the fraction associated with Cdk2), a nuclear protein that is known to inhibit different cyclin-Cdk complexes, are found to decline in the gastric mucosa with advancing age. In contrast, with aging, there was a steady rise in p53 levels in the gastric mucosa. We have also observed that the levels of phosphorylated retinoblastoma protein, a form that participates in regulating progression through the S phase, are markedly elevated in the gastric mucosa of aged rats. In conclusion, our data suggest that, in the gastric mucosa, aging enhances transition of G1 to S phase as well as progression through the S phase of the cell cycle. However, the age-related decline in p21Waf1/Cip1 in the gastric mucosa appears to be independent of p53 status.

scholarly journals Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Indira Pokkunuri ◽  
Quaisar Ali ◽  
Mohammad Asghar
Keyword(s):  
Kidney Function ◽  
Kidney Injury ◽  
Protein Carbonyls ◽  
Aged Rats ◽  
Fischer 344 Rats ◽  
Adult Rats ◽  
Fischer 344 ◽  
Age Related ◽  
Kidney Injury Molecule 1 ◽  
Kidney Functions

We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions.

Cross talk between androgen and Wnt signaling potentially contributes to age-related skeletal muscle atrophy in rats

2018 ◽  
Vol 125 (2) ◽  
pp. 486-494 ◽  
Author(s):  
Petey W. Mumford ◽  
Matthew A. Romero ◽  
Xuansong Mao ◽  
C. Brooks Mobley ◽  
Wesley C. Kephart ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Wnt Signaling ◽  
Muscle Fiber ◽  
Muscle Loss ◽  
Fischer 344 Rats ◽  
Protein Levels ◽  
Fischer 344 ◽  
Age Related ◽  
Fiber Size

We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum-free and total testosterone (TEST) and gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3, 6, 12, 18, and 24 mo (mo) old ( n = 9 per group). Free and total TEST was greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass ( r = 0.395, P = 0.007) as well as AR and Wnt5 protein levels (r = 0.670, P < 0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C2C12-derived myotubes with lower (75 ng/ml) and higher (150 ng/ml) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size ( P < 0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10-mo-old male Fischer 344 rats ( n = 10–11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E); trenbolone enanthate (TREN), a nonaromatizable synthetic testosterone analogue; or a vehicle (ORX only) for 4 wk. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus muscle compared with ORX only ( P < 0.05). To summarize, aromatizable and nonaromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss. NEW & NOTEWORTHY Results from this study demonstrate androgen and Wnt5 protein expression decrease with aging, and this may be a mechanism involved with age-related muscle loss.

scholarly journals Phrenic motor neuron loss in aged rats

2018 ◽  
Vol 119 (5) ◽  
pp. 1852-1862 ◽  
Author(s):  
Matthew J. Fogarty ◽  
Tanya S. Omar ◽  
Wen-Zhi Zhan ◽  
Carlos B. Mantilla ◽  
Gary C. Sieck
Keyword(s):  
Motor Neuron ◽  
Surface Area ◽  
Motor Neurons ◽  
Fiber Type ◽  
Dendritic Morphology ◽  
Diaphragm Muscle ◽  
Specific Force ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Age Related

Sarcopenia is the age-related reduction of muscle mass and specific force. In previous studies, we found that sarcopenia of the diaphragm muscle (DIAm) is evident by 24 mo of age in both rats and mice and is associated with selective atrophy of type IIx and IIb muscle fibers and a decrease in maximum specific force. These fiber type-specific effects of sarcopenia resemble those induced by DIAm denervation, leading us to hypothesize that sarcopenia is due to an age-related loss of phrenic motor neurons (PhMNs). To address this hypothesis, we determined the number of PhMNs in young (6 mo old) and old (24 mo old) Fischer 344 rats. Moreover, we determined age-related changes in the size of PhMNs, since larger PhMNs innervate type IIx and IIb DIAm fibers. The PhMN pool was retrogradely labeled and imaged with confocal microscopy to assess the number of PhMNs and the morphometry of PhMN soma and proximal dendrites. In older animals, there were 22% fewer PhMNs, a 19% decrease in somal surface area, and a 21% decrease in dendritic surface area compared with young Fischer 344 rats. The age-associated loss of PhMNs involved predominantly larger PhMNs. These results are consistent with an age-related denervation of larger, more fatigable DIAm motor units, which are required primarily for high-force airway clearance behaviors. NEW & NOTEWORTHY Diaphragm muscle sarcopenia in rodent models is well described in the literature; however, the relationship between sarcopenia and frank phrenic motor neuron (MN) loss is unexplored in these models. We quantify a 22% loss of phrenic MNs in old (24 mo) compared with young (6 mo) Fischer 344 rats. We also report reductions in phrenic MN somal and proximal dendritic morphology that relate to decreased MN heterogeneity in old compared with young Fischer 344 rats.

Upregulation of G protein-linked receptor kinases with advancing age in rat aorta

2001 ◽  
Vol 280 (3) ◽  
pp. R897-R903 ◽  
Author(s):  
William E. Schutzer ◽  
John F. Reed ◽  
Michael Bliziotes ◽  
Scott L. Mader
Keyword(s):  
G Protein ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Fischer 344 Rats ◽  
Membrane Expression ◽  
Fischer 344 ◽  
Age Related ◽  
Protein Receptor ◽  
Receptor Kinases ◽  
Increased Activity

The age-related decline in β-adrenergic receptor (β-AR)-mediated vasorelaxation is associated with desensitization of β-ARs without significant downregulation. The primary mode of this homologous β-AR desensitization, in general, is via G protein receptor kinases (GRK). Therefore, we hypothesize that age-related changes in GRKs are causative to this etiology in rat aorta. Herein, we investigate the activity and cellular distribution (cytoplasmic vs. membrane) of several GRK isoforms and β-arrestin proteins. GRK activity was assessed in extracts from aortic tissue of 6-wk, 6-mo, 12-mo, and 24-mo-old male Fischer-344 rats using a rhodopsin phosphorylation assay. We also performed immunoblots on lysates from aorta with specific antibodies to GRK-2, -3, -5, and β-arrestin-1. Results show an age-related increase in GRK activity. Furthermore, expression of GRK-2 (cytoplasmic and membrane), GRK-3 (cytoplasmic and membrane), and β-arrestin (soluble) increased with advancing age, whereas GRK-5 (membrane) expression remained unchanged. These results suggest that age is associated with increased activity and expression of specific GRKs. This increase likely results in enhanced phosphorylation and desensitization of β-ARs. These biochemical changes are consistent with observed aging physiology.

Age-related increases in diaphragmatic maximal shortening velocity

1996 ◽  
Vol 80 (2) ◽  
pp. 445-451 ◽  
Author(s):  
S. K. Powers ◽  
D. Criswell ◽  
R. A. Herb ◽  
H. Demirel ◽  
S. Dodd
Keyword(s):  
Force Production ◽  
Specific Force ◽  
Fischer 344 Rats ◽  
Rat Diaphragm ◽  
Shortening Velocity ◽  
Fischer 344 ◽  
Age Related ◽  
Highly Correlated ◽  
Related Increase

Recent evidence demonstrates that aging results in an increase in fast (type IIB) myosin heavy chain (MHC) in the rat diaphragm. It is unknown whether this age-related change in fast MHC influences the diaphragmatic maximal shortening velocity (Vmax). Therefore, we tested the hypothesis that aging is associated with an increase in the diaphragmatic Vmax and that the increase in the Vmax is highly correlated with the percentage of type IIb MHC. In vitro contractile properties were measured with costal diaphragm strips obtained from young (4 mo old; n = 8) and (old 24 mo old; n = 8) male Fischer-344 rats. Diaphragmatic maximal tetanic specific force production was 14.5% lower in the old compared with the young animals (23.0 +/- 0.4 vs. 19.7 +/- 0.8 N/cm2; P < 0.05). In contrast, the diaphragmatic Vmax was significantly higher in the old compared with the young animals (5.5 +/- 0.1 vs. 4.4 +/- 0.3 lengths/s; P < 0.05). Although the percent type IIb MHC was significantly higher (approximately +14%; P < 0.05) in the old compared with the young animals, the correlation between Vmax and percent type IIb MHC was relatively low (r = 0.50; P = 0.05). These data support the hypothesis that an age-related increase in diaphragmatic Vmax occurs; however, factors in addition to type IIb MHC are involved in regulating diaphragmatic Vmax. Interestingly, although aging resulted in a decrease in diaphragmatic maximal specific force production, power output at all muscle loads was maintained in the old animals due to the increase in diaphragmatic shortening velocity.

Age-related immunosenescence in Fischer 344 rats: influence of exercise training

1992 ◽  
Vol 73 (5) ◽  
pp. 1932-1938 ◽  
Author(s):  
I. Nasrullah ◽  
R. S. Mazzeo
Keyword(s):  
Endurance Training ◽  
Interleukin 2 ◽  
Cytolytic Activity ◽  
Treadmill Running ◽  
Target Cells ◽  
Fischer 344 Rats ◽  
Middle Aged ◽  
Fischer 344 ◽  
Age Related ◽  
Old Rats

The present investigation examined the extent to which 15 wk of endurance training could influence immune function in young, middle-aged, and older animals. Forty-eight male Fischer 344 rats were divided into trained and untrained groups. Training consisted of treadmill running at 75% maximal running capacity for 1 h/day, 5 days/wk, for 15 wk. Animals were killed at 8, 17, and 27 mo, at which time splenocytes were isolated. The capacity for lymphocyte proliferation in response to mitogen (concanavalin A, ConA), interleukin-2 (IL-2) production, and cytolytic activity against YAC-1 target cells was determined. ConA-induced proliferation declined significantly with age. Training suppressed the proliferative response in the young (-41%) and middle-aged animals (-27%) compared with the age-matched controls; however, training improved this response (+58%) in the older group. IL-2 production followed a pattern similar to that for mitogen-induced proliferation, such that production declined with age and was reduced with training in young and middle-aged animals but was significantly more improved in the older animals than in age-matched controls. The ability to lyse target cells, measured as percent cytotoxicity, declined steadily with advancing age at all effector-to-target cell ratios tested: 52, 14, and -16% for 8-, 17-, and 27-mo-old rats, respectively. It was concluded that the capacity for ConA-induced splenocyte proliferation, IL-2 production, and cytolytic activity declines significantly with advancing age. Furthermore, 15 wk of endurance training suppressed proliferation and IL-2 production in young animals but improved these responses in older animals. Training had no effect on cytolytic activity.

An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms

1995 ◽  
Vol 268 (4) ◽  
pp. L539-L545 ◽  
Author(s):  
A. T. Canada ◽  
L. A. Herman ◽  
S. L. Young
Keyword(s):  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Fischer 344 Rats ◽  
Fischer 344 ◽  
Related Difference ◽  
Age Related ◽  
65 H ◽  
Old Rats ◽  
Gpx Activity

The role of animal age in the lethal response to > 98% oxygen has been extensively studied, with the observation that neonatal rats were resistant while mature animals were sensitive. Antioxidant enzymes increased during the oxygen exposure in neonatal but not in mature rats, suggesting they were important in the age-related toxicity difference. Because no studies had compared the response of mature and old rats to hyperoxia, we exposed Fischer 344 rats, aged 2 and 27 mo, to > 98% oxygen. Unexpectedly, the old rats lived significantly longer than young, 114 and 65 h, respectively. No histopathological differences were found to explain the results. Of the antioxidants, only glutathione peroxidase (GPx) activity was higher in the lungs of nonexposed old rats. Superoxide dismutase (SOD) was higher in the young, results opposite those expected if SOD was important in the lethality difference. No antioxidant induction occurred in the old oxygen-exposed rats. These results suggest that although there may be a role for GPx, mechanisms in addition to antioxidant protection and inflammation are likely responsible for the age-related difference in hyperoxia lethality.

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