9 Resistance to age-related weight gain is associated with stimulation of skeletal muscle mitochondrial oxidative capacity during caloric restriction in young rats

Although mitochondrial dysfunction has been implicated in aging, physical function decline, and several age-related diseases, an accessible and affordable measure of mitochondrial health is still lacking. In this study we identified the proteomic signature of muscular mitochondrial oxidative capacity in plasma. In 165 adults, we analyzed the association between concentrations of plasma proteins, measured using the SOMAscan assay, and skeletal muscle maximal oxidative phosphorylation capacity assessed as post-exercise phosphocreatine recovery time constant (τPCr) by phosphorous magnetic resonance spectroscopy. Out of 1301 proteins analyzed, we identified 87 proteins significantly associated with τPCr, adjusting for age, sex, and phosphocreatine depletion. Sixty proteins were positively correlated with better oxidative capacity, while 27 proteins were correlated with poorer capacity. Specific clusters of plasma proteins were enriched in the following pathways: homeostasis of energy metabolism, proteostasis, response to oxidative stress, and inflammation. The generalizability of these findings would benefit from replication in an independent cohort and in longitudinal analyses.

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The thioredoxin system in aging muscle: key role of mitochondrial thioredoxin reductase in the protective effects of caloric restriction?

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00890.2005 ◽

2006 ◽

Vol 291 (4) ◽

pp. R927-R935 ◽

Cited By ~ 55

Author(s):

Susanne Rohrbach ◽

Stefanie Gruenler ◽

Mirja Teschner ◽

Juergen Holtz

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Cardiac Muscle ◽

Caloric Restriction ◽

Dna Cleavage ◽

Thioredoxin Reductase ◽

Protective Effects ◽

Young Rats ◽

Age Related ◽

Thioredoxin System

Cellular redox balance is maintained by various antioxidative systems. Among those is the thioredoxin system, consisting of thioredoxin, thioredoxin reductase, and NADPH. In the present study, we examined the effects of caloric restriction (2 mo) on the expression of the cytosolic and mitochondrial thioredoxin system in skeletal muscle and heart of senescent and young rats. Mitochondrial thioredoxin reductase (TrxR2) is significantly reduced in aging skeletal and cardiac muscle and renormalized after caloric restriction, while the cytosolic isoform remains unchanged. Thioredoxins (mitochondrial Trx2, cytosolic Trx1) are not influenced by caloric restriction. In skeletal and cardiac muscle of young rats, caloric restriction has no effect on the expression of thioredoxins or thioredoxin reductases. Enforced reduction of TrxR2 (small interfering RNA) in myoblasts under exposure to ceramide or TNF-α causes a dramatic enhancement of nucleosomal DNA cleavage, caspase 9 activation, and mitochondrial reactive oxygen species release, together with reduced cell viability, while this TrxR2 reduction is without effect in unstimulated myoblasts under basal conditions. Oxidative stress in vitro (H2O2in C2C12myoblasts and myotubes) results in different changes: TrxR2, Trx2, and Trx1 are induced without alterations in the cytosolic thioredoxin reductase isoforms. Thus aging is associated with a TrxR2 reduction in skeletal muscle and heart, which enhances susceptibility to apoptotic stimuli but is renormalized after short-term caloric restriction. Exogenous oxidative stress does not result in these age-related changes of TrxR2.

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Moderate Caloric Restriction, But Not Physiological Hyperleptinemia Per Se, Enhances Mitochondrial Oxidative Capacity in Rat Liver and Skeletal Muscle—Tissue-Specific Impact on Tissue Triglyceride Content and AKT Activation

Endocrinology ◽

10.1210/en.2004-1396 ◽

2005 ◽

Vol 146 (4) ◽

pp. 2098-2106 ◽

Cited By ~ 28

Author(s):

Rocco Barazzoni ◽

Michela Zanetti ◽

Alessandra Bosutti ◽

Gianni Biolo ◽

Laura Vitali-Serdoz ◽

...

Keyword(s):

Skeletal Muscle ◽

Caloric Restriction ◽

Rat Liver ◽

Muscle Tissue ◽

Oxidative Capacity ◽

Akt Activation ◽

Mitochondrial Oxidative Capacity ◽

Triglyceride Content ◽

Per Se ◽

Specific Impact

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Faculty Opinions recommendation of Combined effects of ghrelin and higher food intake enhance skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rats with chronic kidney disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1344956.816054 ◽

2009 ◽

Author(s):

Carolyn Ecelbarger

Keyword(s):

Skeletal Muscle ◽

Chronic Kidney Disease ◽

Food Intake ◽

Kidney Disease ◽

Oxidative Capacity ◽

Combined Effects ◽

Akt Phosphorylation ◽

Mitochondrial Oxidative Capacity

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Caloric restriction increases muscle and liver mitochondrial oxidative capacity in young but not in old rats

Clinical Nutrition ◽

10.1016/s0261-5614(03)80160-7 ◽

2003 ◽

Vol 22 ◽

pp. S43

Author(s):

R. Barazzoni ◽

M. Zanetti ◽

L. Visintin ◽

G. Biolo ◽

M. Stebel ◽

...

Keyword(s):

Caloric Restriction ◽

Oxidative Capacity ◽

Mitochondrial Oxidative Capacity ◽

Old Rats

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Age-related loss of calcitriol stimulation of phosphoinositide hydrolysis in rat skeletal muscle

Molecular and Cellular Endocrinology ◽

10.1016/s0303-7207(97)00221-9 ◽

1998 ◽

Vol 136 (2) ◽

pp. 131-138 ◽

Cited By ~ 10

Author(s):

Maria Marta Facchinetti ◽

Ricardo Boland ◽

Ana R de Boland

Keyword(s):

Skeletal Muscle ◽

Phosphoinositide Hydrolysis ◽

Rat Skeletal Muscle ◽

Age Related ◽

Stimulation Of

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Short term intensified training temporarily impairs mitochondrial respiratory capacity in elite endurance athletes

Journal of Applied Physiology ◽

10.1152/japplphysiol.00829.2020 ◽

2021 ◽

Author(s):

Daniele A. Cardinale ◽

Kasper D. Gejl ◽

Kristine Grøsfjeld Petersen ◽

Joachim Nielsen ◽

Niels Ørtenblad ◽

...

Keyword(s):

Skeletal Muscle ◽

Quality Control ◽

Oxidative Capacity ◽

Endurance Athletes ◽

Training Period ◽

Moderate Intensity ◽

Mitochondrial Quality Control ◽

Quality Control Program ◽

Mitochondrial Oxidative Capacity ◽

Mitochondrial Respiratory

Aim: The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program which includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption and performance in highly trained endurance athletes. Methods: 27 elite endurance athletes performed high intensity interval exercise followed by moderate intensity continuous exercise 3 days per week for 4 weeks in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period. Results: The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ~20 % lower after training although some markers of mitochondrial density increased by 5-50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase, was doubled. Conclusion: Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training while mitochondrial quality control is slightly activated in highly trained skeletal muscle.

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Sexual dimorphism in liver mitochondrial oxidative capacity is conserved under caloric restriction conditions

AJP Cell Physiology ◽

10.1152/ajpcell.00203.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. C1302-C1308 ◽

Cited By ~ 50

Author(s):

A. Valle ◽

R. Guevara ◽

F. J. García-Palmer ◽

P. Roca ◽

J. Oliver

Keyword(s):

Sexual Dimorphism ◽

Energy Expenditure ◽

Oxidative Damage ◽

Caloric Restriction ◽

Oxidative Capacity ◽

Complex Iii ◽

Female Rats ◽

Oxidative Balance ◽

Wide Range ◽

Mitochondrial Oxidative Capacity

Caloric restriction (CR) without malnutrition has been shown to increase maximal life span and delay the rate of aging in a wide range of species. It has been proposed that reduction in energy expenditure and oxidative damage may explain the life-extending effect of CR. Sex-related differences also have been shown to influence longevity and energy expenditure in many mammalian species. The aim of the present study was to determine the sex-related differences in rat liver mitochondrial machinery, bioenergetics, and oxidative balance in response to short-term CR. Mitochondria were isolated from 6-mo-old male and female Wistar rats fed ad libitum or subjected to 40% CR for 3 mo. Mitochondrial O2 consumption, activities of the oxidative phosphorylation system (complexes I, III, IV, and V), antioxidative activities [MnSOD, glutathione peroxidase (GPx)], mitochondrial DNA and protein content, mitochondrial H2O2 production, and markers of oxidative damage, as well as cytochrome C oxidase and mitochondrial transcription factor A levels, were measured. Female rats showed a higher oxidative capacity and GPx activity than males. This sexual dimorphism was not modified by CR. Restricted rats showed slightly increased oxygen consumption, complex III activity, and GPx antioxidant activity together with lower levels of oxidative damage. In conclusion, the sexual dimorphism in liver mitochondrial oxidative capacity was unaffected by CR, with females showing higher mitochondrial functionality and ROS protection than males.

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