scholarly journals Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading

2008 ◽  
Vol 105 (6) ◽  
pp. 1695-1705 ◽  
Author(s):  
Parco M. Siu ◽  
Emidio E. Pistilli ◽  
Stephen E. Alway
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Young Adult ◽  
Gastrocnemius Muscle ◽  
Medial Gastrocnemius ◽  
Brown Norway ◽  
Aged Rats ◽  
Muscle Weight ◽  
Animal Body ◽  
Age Dependent

Oxidative stress increases during unloading in muscle from young adult rats. The present study examined the markers of oxidative stress and antioxidant enzyme gene and protein expressions in medial gastrocnemius muscles of aged and young adult (30 and 6 mo of age) Fischer 344 × Brown Norway rats after 14 days of hindlimb suspension. Medial gastrocnemius muscle weight was decreased by ∼30% in young adult and aged rats following suspension. When muscle weight was normalized to animal body weight, it was reduced by 12% and 22% in young adult and aged rats, respectively, after suspension. Comparisons between young adult and aged control animals demonstrated a 25% and 51% decline in muscle mass when expressed as absolute muscle weight and muscle weight normalized to the animal body weight, respectively. H2O2 content was elevated by 43% while Mn superoxide dismutase (MnSOD) protein content was reduced by 28% in suspended muscles compared with control muscles exclusively in the aged animals. Suspended muscles had greater content of malondialdehyde (MDA)/4-hydroxyalkenals (4-HAE) (29% and 58% increase in young adult and aged rats, respectively), nitrotyrosine (76% and 65% increase in young adult and aged rats, respectively), and catalase activity (69% and 43% increase in young adult and aged rats, respectively) relative to control muscles. Changes in oxidative stress markers MDA/4-HAE, H2O2, and MnSOD protein contents in response to hindlimb unloading occurred in an age-dependent manner. These findings are consistent with the hypotheses that oxidative stress has a role in mediating disuse-induced and sarcopenia-associated muscle losses. Our data suggest that aging may predispose skeletal muscle to increased levels of oxidative stress both at rest and during unloading.

Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats

2005 ◽  
Vol 289 (4) ◽  
pp. R1015-R1026 ◽  
Author(s):  
Parco M. Siu ◽  
Emidio E. Pistilli ◽  
Stephen E. Alway
Keyword(s):  
Young Adult ◽  
Cytochrome C ◽  
Gastrocnemius Muscle ◽  
Age Groups ◽  
Medial Gastrocnemius ◽  
Hindlimb Suspension ◽  
Brown Norway ◽  
Aged Rats ◽  
Wet Weight ◽  
Gastrocnemius Muscles

Although apoptosis has been demonstrated in soleus during hindlimb suspension (HS), it is not known whether apoptosis is also involved in the loss of muscles dominated by mixed fibers. Therefore, we examined the apoptotic responses in gastrocnemius muscles of young adult and aged Fischer 344 × Brown Norway rats after 14 days of HS. The medial gastrocnemius muscle wet weight significantly decreased by 30 and 32%, and muscle wet weight normalized to the animal body weight decreased by 11 and 15% in young adult and aged animals, respectively, after HS. The extent of apoptotic DNA fragmentation increased by 119 and 61% in suspended muscles from young and aged rats, respectively. Bax mRNA increased by 73% in young muscles after HS. Bax and Bcl-2 protein levels were greater in suspended muscles relative to control muscles in both age groups. The level of cytosolic mitochondria-housed apoptotic factor cytochrome c was significantly increased in the mitochondria-free cytosol of suspended muscles from young and aged rats. In contrast, the release/accumulation of AIF, a caspase-independent apoptogenic factor, was exclusively expressed in the suspended muscles from aged rats. Our data also show that aging favors the proapoptotic signaling in skeletal muscle by altering the contents of Bax, Bcl-2, Apaf-1, AIF, caspases, XIAP, Smac/DIABLO, and cytochrome c. Furthermore, these results indicate that apoptosis occurs not only in slow-twitch soleus muscle but also in the mixed-fiber (predominately fast fibered) gastrocnemius muscle. Our data are consistent with the hypothesis that apoptotic signaling differs in young adult and aged gastrocnemius muscles during HS.

Hindlimb unloading increases muscle content of cytosolic but not nuclear Id2 and p53 proteins in young adult and aged rats

2006 ◽  
Vol 100 (3) ◽  
pp. 907-916 ◽  
Author(s):  
Parco M. Siu ◽  
Emidio E. Pistilli ◽  
Zsolt Murlasits ◽  
Stephen E. Alway
Keyword(s):  
Young Adult ◽  
Muscle Atrophy ◽  
Gastrocnemius Muscle ◽  
Hindlimb Unloading ◽  
Medial Gastrocnemius ◽  
Hindlimb Suspension ◽  
Aged Rats ◽  
Control Muscle ◽  
Mrna Content ◽  
Wet Weight

This study tested the hypothesis that inhibitor of differentiation-2 (Id2), p53, and heat shock proteins (HSP) are responsive to suspension-induced muscle atrophy. Fourteen days of hindlimb suspension were used to unload the hindlimbs and induce atrophy in gastrocnemius muscles of young adult and aged rats. Following suspension, medial gastrocnemius muscle wet weight was reduced by ∼30%, and the muscle wet weight normalized to the animal body weight decreased by 11 and 15% in young adult and aged animals, respectively. mRNA abundances of Id2, p53, HSP70–2, and HSP27 did not change with suspension, whereas HSP70–1 mRNA content was lower in the suspended muscle compared with the control muscle in both young adult and aged animals. Our immunoblot analyses indicated that protein expressions of HSP70 and HSP60 were not different between suspended and control muscles in both ages, whereas HSP27 protein content was increased in suspended muscle relative to control muscle only in young adult animals. Id2 and p53 protein contents were elevated in the cytosolic fraction of suspended muscle compared with the control muscle in both young and aged animals, but these changes were not found in the nuclear protein fraction. Furthermore, compared with young adult, aged muscles had a lower HSP70–1 mRNA content but higher HSP70–2 mRNA content and protein contents of Id2, p53, HSP70, and HSP27. These findings are consistent with the hypothesis that Id2 and p53 are responsive to unloading-induced muscle atrophy. Moreover, our data indicate that aging is accompanied with altered abundances of HSP70–1 and HSP70–2 mRNA, in addition to Id2, p53, HSP70, and HSP27 protein in rat gastrocnemius muscle.

Effect of growth hormone on gastrocnemius muscle of aged rats after immobilization: biochemistry and morphology

1993 ◽  
Vol 75 (4) ◽  
pp. 1529-1535 ◽  
Author(s):  
E. Carmeli ◽  
Z. Hochberg ◽  
E. Livne ◽  
I. Lichtenstein ◽  
C. Kestelboim ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gastrocnemius Muscle ◽  
Muscle Protein ◽  
Aged Rats ◽  
Muscle Weight ◽  
Hindlimb Muscles ◽  
Capillary Blood Volume ◽  
Rat Growth ◽  
Old Rats ◽  
Limb Immobilization

Immobilization of limbs of aged animals is associated with swift muscular damage and atrophy. We investigated the effect of rat growth hormone (rGH) on immobilized hindlimb muscles of 26-mo-old rats. Administration of rGH significantly reduced muscle weight loss and muscle protein oxidation caused by immobilization. Capillary blood volume, measured by photoplethysmography of the hindlimb, showed a 34% reduction in immobilized animals, which was eliminated by rGH. The activity of creatine phosphokinase in immobilized gastrocnemius muscle was significantly reduced by immobilization. This damage was diminished by rGH administration. Similarly, the increase in acid phosphatase activity in immobilized muscle was reduced after rGH treatment. Morphologically, marked muscle atrophy and fiber disorientation were observed in immobilized limbs. Therapy with rGH prevented some of these changes. These results indicate that administration of rGH may provide a useful means to attenuate the degenerative effects of limb immobilization of aged rats, as evident from physiological, biochemical, and morphological parameters.

scholarly journals Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 648 ◽  
Author(s):  
Adil El Midaoui ◽  
I. George Fantus ◽  
Ali Ait Boughrous ◽  
Réjean Couture
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Body Weight ◽  
Gastrocnemius Muscle ◽  
Antioxidant Properties ◽  
Visceral Obesity ◽  
Adipocyte Hypertrophy ◽  
Zdf Rats ◽  
Protein Staining ◽  
O2 Production

Evidence suggests that oxidative stress plays a major role in the development of metabolic syndrome. This study aims to investigate whether α-lipoic acid (LA), a potent antioxidant, could exert beneficial outcomes in Zucker diabetic fatty (ZDF) rats. Male 6-week-old ZDF rats and their lean counterparts (ZL) were fed for six weeks with a standard diet or a chow diet supplemented with LA (1 g/kg feed). At 12 weeks of age, ZDF rats exhibited an increase in systolic blood pressure, epididymal fat weight per body weight, hyperglycemia, hyperinsulinemia, insulin resistance (HOMA index), adipocyte hypertrophy and a rise in basal superoxide anion (O2•−) production in gastrocnemius muscle and a downregulation of epididymal uncoupled protein-1 (UCP-1) protein staining. Treatment with LA prevented the development of hypertension, the rise in whole body weight and O2•− production in gastrocnemius muscle, but failed to affect insulin resistance, hyperglycemia and hyperinsulinemia in ZDF rats. LA treatment resulted in a noticeable increase of pancreatic weight and a further adipocyte hypertrophy, along with a decrease in epididymal fat weight per body weight ratio associated with an upregulation of epididymal UCP-1 protein staining in ZDF rats. These findings suggest that LA was efficacious in preventing the development of hypertension, which could be related to its antioxidant properties. The anti-visceral obesity effect of LA appears to be mediated by its antioxidant properties and the induction of UCP-1 protein at the adipose tissue level in ZDF rats. Disorders of glucose metabolism appear, however, to be mediated by other unrelated mechanisms in this model of metabolic syndrome.

Anatomic capillarization is maintained in relative excess of fiber oxidative capacity in some skeletal muscles of late middle-aged rats

2004 ◽  
Vol 96 (6) ◽  
pp. 2257-2264 ◽  
Author(s):  
Russell T. Hepple ◽  
Janis E. Vogell
Keyword(s):  
Young Adult ◽  
Skeletal Muscles ◽  
Oxidative Capacity ◽  
Brown Norway ◽  
Aged Rats ◽  
Middle Aged ◽  
White Region ◽  
Wide Range ◽  
The Individual ◽  
Gastrocnemius Muscles

The anatomic size of the capillary-to-fiber (C/F) interface plays an important role in O2 flux from blood to tissue by determining the surface area available for diffusion and is maintained in relative proportion to fiber mitochondrial volume across a wide range of muscle aerobic capacity. In the present study, we examined an estimate of the anatomic size of the C/F interface [the quotient of the individual C/F ratio and fiber perimeter, C/F perimeter exchange (CFPE) index] and fiber oxidative capacity in different skeletal muscles, or muscle regions, to test the hypothesis that capillarization would be maintained in relative excess of reduced fiber oxidative capacity in aged muscles. The right gastrocnemius, plantaris, and soleus muscles from young adult (8 mo old) and late middle-aged (28–30 mo old) Fischer 344 × Brown Norway F1 hybrid rats were excised for evaluation of flux through electron transport chain complexes I–III and/or morphometric estimation of capillarization. Muscle mass was lower in the gastrocnemius muscles of the older animals (2,076 ± 32 vs. 1,825 ± 47 mg in young adult vs. late middle-aged, respectively; mean ± SE) but not the plantaris or soleus muscles. Fibers were smaller in the white region of gastrocnemius muscles but larger in the red region of gastrocnemius muscles of the older animals. There was no difference in the number of capillaries around a fiber, the individual C/F ratio, or the CFPE index between groups for any muscle/region, whereas flux through complexes I–III was reduced by 29–43% in late middle-aged animals. Thus the greater quotient of indexes of anatomic capillarity (individual C/F ratio or CFPE index) and fiber oxidative capacity in soleus and the white region of gastrocnemius muscles, but not in the red region of gastrocnemius muscles of the older animals, shows that anatomic capillarity is maintained in relative excess of oxidative capacity in some muscle regions in late middle-aged rats.

scholarly journals The hypothalamus to brainstem circuit suppresses late-onset body weight gain

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuko Maejima ◽  
Shigeki Kato ◽  
Shoichiro Horita ◽  
Yoichi Ueta ◽  
Seiichi Takenoshita ◽  
...  
Keyword(s):  
Body Weight ◽  
Neural Circuits ◽  
Late Onset ◽  
Body Weight Gain ◽  
Growth Period ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Aged Rats ◽  
Age Dependent ◽  
The Brain

AbstractBody weight (BW) is regulated in age-dependent manner; it continues to increase during growth period, and reaches a plateau once reaching adulthood. However, its underlying mechanism remains unknown. Regarding such mechanisms in the brain, we here report that neural circuits from the hypothalamus (paraventricular nucleus: PVN) to the brainstem (dorsal vagal complex: DVC) suppress late-onset BW gain without affecting food intake. The genetic suppression of the PVN-DVC circuit induced BW increase only in aged rats, indicating that this circuit contributes to suppress the BW at a fixed level after reaching adulthood. PVN neurons in the hypothalamus were inactive in younger rats but active in aged rats. The density of neuropeptide Y (NPY) terminal/fiber is reduced in the aged rat PVN area. The differences in neuronal activity, including oxytocin neurons in the PVN, were affected by the application of NPY or its receptor inhibitor, indicating that NPY is a possible regulator of this pathway. Our data provide new insights into understanding age-dependent BW regulation.

scholarly journals Increased myogenic repressor Id mRNA and protein levels in hindlimb muscles of aged rats

2002 ◽  
Vol 282 (2) ◽  
pp. R411-R422 ◽  
Author(s):  
Stephen E. Alway ◽  
Hans Degens ◽  
Dawn A. Lowe ◽  
Gururaj Krishnamurthy
Keyword(s):  
Young Adult ◽  
Mrna Level ◽  
Brown Norway ◽  
Mrna Levels ◽  
Aged Rats ◽  
Adult Rats ◽  
Protein Levels ◽  
Fast And Slow Muscles ◽  
Hindlimb Muscles ◽  
Gastrocnemius Muscles

The objective of this study was to determine if levels of repressors to myogenic regulatory factors (MRFs) differ between muscles from young adult and aged animals. Total RNA from plantaris, gastrocnemius, and soleus muscles of Fischer 344 × Brown Norway rats aged 9 mo (young adult, n = 10) and 37 mo (aged, n = 10) was reverse transcribed and then amplified by PCR. To obtain a semiquantitative measure of the mRNA levels, PCR signals were normalized to cyclophilin or 18S signals from the corresponding reverse transcription product. Normalization to cyclophilin and 18S gave similar results. The mRNA levels of MyoD and myogenin were ∼275–650% ( P < 0.001) and ∼500–1,100% ( P < 0.001) greater, respectively, in muscles from aged compared with young adults. In contrast, the protein levels were lower in plantaris and gastrocnemius muscles and similar in the soleus muscle of aged vs. young adult rats. Id repressor mRNA levels were ∼300–900% greater in fast and slow muscles of aged animals ( P ≤ 0.02), and Mist 1 mRNA was ∼50% greater in the plantaris and gastrocnemius muscles ( P< 0.01). The mRNA level of Twist mRNA was not significantly affected by aging. Id-1, Id-2, and Id-3 protein levels were ∼17–740% greater ( P < 0.05) in hindlimb muscles of aged rats compared with young adult rats. The elevated levels of Id mRNA and protein suggest that MRF repressors may play a role in gene regulation of fast and slow muscles in aged rats.

Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

2011 ◽  
Vol 256 (3) ◽  
pp. 386-398 ◽  
Author(s):  
Prasada Rao S. Kodavanti ◽  
Joyce E. Royland ◽  
Judy E. Richards ◽  
Jonathan Besas ◽  
Robert C. MacPhail
Keyword(s):  
Oxidative Stress ◽  
Young Adult ◽  
Middle Age ◽  
Brain Regions ◽  
Brown Norway ◽  
Norway Rats
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