scholarly journals Age-Related Mitochondrial Impairment and Renal Injury Is Ameliorated by Sulforaphane via Activation of Transcription Factor NRF2

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 156
Author(s):  
Razia Sultana Mohammad ◽  
Mustafa F. Lokhandwala ◽  
Anees A. Banday
Keyword(s):  
Transcription Factor ◽  
Mitochondrial Function ◽  
Redox Homeostasis ◽  
Fischer 344 Rats ◽  
Kidney Dysfunction ◽  
Fischer 344 ◽  
Mitochondrial Impairment ◽  
Age Related ◽  
Nrf2 Expression

Age is one of the major risk factors for the development of chronic pathologies, including kidney diseases. Oxidative stress and mitochondrial dysfunction play a pathogenic role in aging kidney disease. Transcription factor NRF2, a master regulator of redox homeostasis, is altered during aging, but the exact implications of altered NRF2 signaling on age-related renal mitochondrial impairment are not yet clear. Herein, we investigated the role of sulforaphane, a well-known NRF2 activator, on age-related mitochondrial and kidney dysfunction. Young (2–4 month) and aged (20–24 month) male Fischer 344 rats were treated with sulforaphane (15 mg/kg body wt/day) in drinking water for four weeks. We observed significant impairment in renal cortical mitochondrial function along with perturbed redox homeostasis, decreased kidney function and marked impairment in NRF2 signaling in aged Fischer 344 rats. Sulforaphane significantly improved mitochondrial function and ameliorated kidney injury by increasing cortical NRF2 expression and activity and decreasing protein expression of KEAP1, an NRF2 repressor. Sulforaphane treatment did not affect the renal NRF2 expression or activity and mitochondrial function in young rats. Taken together, our results provide novel insights into the protective role of the NRF2 pathway in kidneys during aging and highlight the therapeutic potential of sulforaphane in mitigating kidney dysfunction in elders.

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.

The role of mitochondrial DNA large deletion for the development of presbycusis in Fischer 344 rats

2007 ◽  
Vol 27 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Shankai Yin ◽  
Zhiping Yu ◽  
Ravi Sockalingam ◽  
Manohar Bance ◽  
Genlou Sun ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Large Deletion ◽  
Fischer 344 Rats ◽  
Fischer 344

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.

Role of spontaneous interstitial cell testicular tumors on the mitogen reactivity of spleen cells from aged male fischer-344 rats

1984 ◽  
Vol 25 (3) ◽  
pp. 349-353 ◽  
Author(s):  
Richard J. Cross ◽  
Jean C. Jackson ◽  
Thomas L. Roszman ◽  
William H. Brooks ◽  
William R. Markesbery
Keyword(s):  
Interstitial Cell ◽  
Fischer 344 Rats ◽  
Spleen Cells ◽  
Testicular Tumors ◽  
Fischer 344

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.

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.

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