Comparative Analyses of mTOR/Akt and Muscle Atrophy-Related Signaling in Aged Respiratory and Gastrocnemius Muscles

Sarcopenia is the degenerative loss of skeletal muscle mass and function associated with aging and occurs in the absence of any underlying disease or condition. A comparison of the age-related molecular signaling signatures of different muscles has not previously been reported. In this study, we compared the age-related molecular signaling signatures of the intercostal muscles, the diaphragm, and the gastrocnemii using 6-month and 20-month-old rats. The phosphorylation of Akt, ribosomal S6, and Forkhead box protein O1 (FoxO1) in diaphragms significantly increased with age, but remained unchanged in the intercostal and gastrocnemius muscles. In addition, ubiquitin-proteasome degradation, characterized by the levels of MuRF1 and Atrogin-1, did not change with age in all rat muscles. Interestingly, an increase in LC3BII and p62 levels marked substantial blockage of autophagy in aged gastrocnemii but not in aged respiratory muscles. These changes in LC3BII and p62 levels were also associated with a decrease in markers of mitochondrial quality control. Therefore, our results suggest that the age-related signaling events in respiratory muscles differ from those in the gastrocnemii, most likely to preserve the vital functions played by the respiratory muscles.

Download Full-text

Chlorella vulgaris Ameliorates Oxidative Stress and Improves the Muscle Regenerative Capacity of Young and Old Sprague-Dawley Rats

Nutrients ◽

10.3390/nu12123752 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3752

Author(s):

Nurhazirah Zainul Azlan ◽

Yasmin Anum Mohd Yusof ◽

Suzana Makpol

Keyword(s):

Oxidative Stress ◽

Muscle Mass ◽

Chlorella Vulgaris ◽

Untreated Control ◽

Oxidative Stress Marker ◽

Sprague Dawley ◽

Old Rats ◽

Group 2 ◽

And Function ◽

Gastrocnemius Muscles

Muscle atrophy in ageing is a multifactorial degenerative process impacted by cellular ageing biology, which includes oxidative stress. Chlorella vulgaris is a coccoid green eukaryotic microalga rich in antioxidants. The aim of this study was to determine the effect of C. vulgaris in ameliorating oxidative stress, thus elucidating its mechanism in improving muscle mass, strength and function in young and old rats. Fifty-six male Sprague-Dawley (SD) rats aged 3 months (young) and 21 months (old) were divided into three groups: Group 1 (control) was given distilled water; Group 2 was treated with 150 mg/kg body weight (BW) of C. vulgaris; and Group 3 was treated with 300 mg/kg BW of C. vulgaris for three months. Grip and muscle strength and muscle integrity were determined on days 0, 30, 60, and 90 of treatment. Urine and blood were collected on days 0 and 90 of treatment for oxidative stress marker determination, while the gastrocnemius muscles were collected for muscle oxidative stress analysis. Increased grip strength of the front and hind paws was observed in young C. vulgaris-treated rats on days 30, 60, and 90 compared to the untreated control on the same days (p < 0.05). There was a significant increase in lean bone mineral content (BMC) in young rats treated with 300 mg/kg BW C. vulgaris compared to untreated rats on days 30 and 60. The fat mass was significantly decreased in young and old C. vulgaris-treated rats on day 90 compared to the untreated control. The total path was significantly increased for old rats treated with 300 mg/kg BW C. vulgaris on days 60 and 90 compared to day 0. Young and old C. vulgaris-treated rats demonstrated a significant decrease in urinary isoprostane F2t and plasma creatine kinase-MM (CKMM) compared to the control on day 90. A significant decrease in malondialdehyde (MDA) and 4-hydroxyalkenal (HAE) levels were observed in young and old rats treated with C. vulgaris. C. vulgaris improved the muscle mass, strength, and function in young and old rats. This effect could be due to its potency in ameliorating oxidative stress in the skeletal muscle of young and old rats.

Download Full-text

Analysis of the Molecular Signaling Signatures of Muscle Protein Wasting Between the Intercostal Muscles and the Gastrocnemius Muscles in db/db Mice

International Journal of Molecular Sciences ◽

10.3390/ijms20236062 ◽

2019 ◽

Vol 20 (23) ◽

pp. 6062 ◽

Cited By ~ 1

Author(s):

Kun Woo Kim ◽

Mi-Ock Baek ◽

Ji-Young Choi ◽

Kuk Hui Son ◽

Mee-Sup Yoon

Keyword(s):

Gastrocnemius Muscle ◽

Muscle Wasting ◽

Muscle Protein ◽

Respiratory Muscles ◽

Diabetic Mouse ◽

Molecular Signaling ◽

Akt Phosphorylation ◽

Intercostal Muscles ◽

The Difference ◽

Gastrocnemius Muscles

Type 2 diabetes (T2D) patients suffer from dyspnea, which contributes to disease-related morbidity. Although T2D has been reported to induce a catabolic state in skeletal muscle, whether T2D induces muscle wasting in respiratory muscles has not yet been investigated. In this study, we examine the difference in the molecular signaling signature of muscle wasting between the intercostal and gastrocnemius muscles using db/db mice, a well-known diabetic mouse model. Akt phosphorylation was significantly decreased in both the intercostal and gastrocnemius muscles of db/db mice and was accompanied by a decrease in mTORC1 activity. In addition, FoxO phosphorylation was suppressed, and ubiquitin-proteasome degradation, characterized by the level of Atrogin-1 and MuRF1, was subsequently enhanced in both muscle types of db/db mice. An increase in LC3BII levels and a decrease in p62 levels marked the occurrence of substantial autophagy in the gastrocnemius muscle but not in the intercostal muscles of db/db mice. Therefore, we suggest that the signaling events of muscle wasting in the intercostal muscles of db/db mice are different from those in the gastrocnemius muscle of db/db mice.

Download Full-text

Structure and function changes in rat adrenal glands during aging

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.255.6.e903 ◽

1988 ◽

Vol 255 (6) ◽

pp. E903-E911 ◽

Cited By ~ 2

Author(s):

E. Reaven ◽

M. Kostrna ◽

J. Ramachandran ◽

S. Azhar

Keyword(s):

Adrenal Gland ◽

Plasma Volume ◽

Endocrine Cells ◽

Structural Changes ◽

Adrenal Weight ◽

Hormone Production ◽

Age Related ◽

Old Rats ◽

And Function ◽

Serum Acth

The current study examines corticosterone production in young and old rats with a view to understanding how hormone production is related to aging changes in the adrenal gland. For this purpose, we compared total (plasma volume-corrected) values for adrenocorticotropic hormone (ACTH)-induced maximal corticosterone production in young, mature (5-mo-old), and aging (18-mo-old) rats. These values were subsequently corrected for measured age-related differences in adrenal weight, adrenal cortex volume, specific adrenal zone volumes, and total number of corticosterone-producing cells in the adrenals of the differently aged rats. In addition, corticosterone disposal rates were measured in the two groups of rats, and adrenal cortical ACTH binding sites were identified by autoradiography after perfusion with 125I-labeled ACTH analogue. The results show that maximal serum ACTH-induced corticosterone concentrations (per ml serum) in the 18-mo-old rats are somewhat less than those seen in the younger animals. However, because the plasma volume is greater in the older animals (and corticosterone disposal rates do not vary), total circulating corticosterone production is, in fact, equivalent in the two groups of animals. When these total values for corticosterone are corrected for various structural changes in the adrenal gland with age, corticosterone production was found to be lower in the older group of rats: i.e., one sees an approximately 50% decline when corticosterone is expressed per adrenal weight or zonal volume and an approximately 20% decline when expressed per number of endocrine cells per adrenal.(ABSTRACT TRUNCATED AT 250 WORDS)

Download Full-text

Food Restriction Prevents Advanced Glycation End Product Accumulation and Retards Kidney Aging in Lean Rats

Journal of the American Society of Nephrology ◽

10.1681/asn.v1181488 ◽

2000 ◽

Vol 11 (8) ◽

pp. 1488-1497

Author(s):

LAURENT TEILLET ◽

PHILIPPE VERBEKE ◽

SABINE GOURAUD ◽

HILAIRE BAKALA ◽

CAROLINE BOROT-LALOI ◽

...

Keyword(s):

Food Restriction ◽

Structure And Function ◽

Female Rats ◽

Advanced Glycation ◽

Age Related ◽

Glycation End Products ◽

Old Rats ◽

Cardiovascular Systems ◽

And Function ◽

Chronic Food Restriction

Abstract.Tissue content of advanced glycation end products (AGE) increases with age and contributes to the changes in structure and function of the renal and cardiovascular systems. The effect of chronic food restriction on this AGE accumulation was investigated in lean WAG/Rij rats. A 30% food restriction performed from 10 to 30 mo in female rats reduced their mean body weight from 240 ± 7 to 160 ± 12 g, but did not modify their survival. AGE collagen content increased from 14.3 ± 5.5 to 104.7 ± 13.0 arbitrary units per microgram (AU/μg) of hydroxyproline (OHPro) in kidney between 10 and 30 mo, and from 9.7 ± 1.2 to 310.6 ± 34.6 AU/μg OHPro in the abdominal aorta. Food restriction reduced AGE accumulation to 21.4 ± 3.3 and 74.6 ± 16.5 AU/μg OHPro in kidney and aorta of 30-mo-old animals. Similar results were found for collagen prepared from isolated glomeruli (7.8 ± 1.2, 81.2 ± 16.1, and 10.3 ± 4.3 AU/μg OHPro in 10-mo, 30-mo, and restricted 30-mo-old rats). Reduction of intrarenal and arterial AGE accumulation by food restriction was confirmed by immunostaining in optical microscopy. Age-related changes in arterial and kidney structures as polyuria and proteinuria were mainly prevented by food restriction. These data indicate that chronic food restriction reduces the accumulation of AGE and preserves the structure and function of the renal and cardiovascular systems in learn rats, although it did not affect survival of the animals between 10 and 30 mo.

Download Full-text

Age-associated breathlessness

Oxford Textbook of Geriatric Medicine ◽

10.1093/med/9780198701590.003.0146 ◽

2017 ◽

pp. 1129-1132

Author(s):

Chang Won Won ◽

Sunyoung Kim

Keyword(s):

Elevated Level ◽

Respiratory Muscles ◽

Underlying Disease ◽

Specific Marker ◽

Common Symptom ◽

Small Airways ◽

Elastic Recoil ◽

Age Related ◽

The Impact

Breathlessness in older adults is a common symptom of cardiovascular, respiratory diseases, psychological disorders such as panic disorder, and respiratory muscle weakness, but this symptom is also prevalent during daily activities as a result of age-related changes. With ageing, physical fitness, the strength of respiratory muscles and elastic recoil of the small airways all decline, and, as a result, breathing becomes more difficult and gas exchange less efficient. Differentiation between cardiac and pulmonary cause of dyspneoa is very important and sometimes difficult. In acutely breathless elderly patients, an elevated level of brain natriuretic peptide is a sensitive and specific marker for the presence of ventricular failure. Once a diagnosis is made, the reversible factors contributing to the breathlessness should be corrected as far as possible, and the initial focus should be on optimizing treatment of the patient’s underlying disease, followed by reducing the impact of breathless on everyday activities and quality of life.

Download Full-text

It Is All about (U)biquitin: Role of Altered Ubiquitin-Proteasome System and UCHL1 in Alzheimer Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/2756068 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 43

Author(s):

Antonella Tramutola ◽

Fabio Di Domenico ◽

Eugenio Barone ◽

Marzia Perluigi ◽

D. Allan Butterfield

Keyword(s):

Oxidative Stress ◽

Alzheimer Disease ◽

Ubiquitin Proteasome System ◽

Oxidative Modification ◽

Age Related ◽

Ubiquitin Proteasome ◽

Proteasome Pathway ◽

And Function ◽

Cellular Components

Free radical-mediated damage to macromolecules and the resulting oxidative modification of different cellular components are a common feature of aging, and this process becomes much more pronounced in age-associated pathologies, including Alzheimer disease (AD). In particular, proteins are particularly sensitive to oxidative stress-induced damage and these irreversible modifications lead to the alteration of protein structure and function. In order to maintain cell homeostasis, these oxidized/damaged proteins have to be removed in order to prevent their toxic accumulation. It is generally accepted that the age-related accumulation of “aberrant” proteins results from both the increased occurrence of damage and the decreased efficiency of degradative systems. One of the most important cellular proteolytic systems responsible for the removal of oxidized proteins in the cytosol and in the nucleus is the proteasomal system. Several studies have demonstrated the impairment of the proteasome in AD thus suggesting a direct link between accumulation of oxidized/misfolded proteins and reduction of this clearance system. In this review we discuss the impairment of the proteasome system as a consequence of oxidative stress and how this contributes to AD neuropathology. Further, we focus the attention on the oxidative modifications of a key component of the ubiquitin-proteasome pathway, UCHL1, which lead to the impairment of its activity.

Download Full-text

Differential Dose- and Tissue-Dependent Effects of foxo on Aging, Metabolic and Proteostatic Pathways

Cells ◽

10.3390/cells10123577 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3577

Author(s):

Maria S. Manola ◽

Sentiljana Gumeni ◽

Ioannis P. Trougakos

Keyword(s):

Accelerated Aging ◽

Model Organisms ◽

Dependent Manner ◽

Forkhead Box ◽

Age Related ◽

Wide Range ◽

Transgenic Lines ◽

Ubiquitin Proteasome ◽

Increased Sensitivity ◽

Proteasome Pathway

Aging is the gradual deterioration of physiological functions that culminates in death. Several studies across a wide range of model organisms have revealed the involvement of FOXO (forkhead box, class O) transcription factors in orchestrating metabolic homeostasis, as well as in regulating longevity. To study possible dose- or tissue-dependent effects of sustained foxo overexpression, we utilized two different Drosophila transgenic lines expressing high and relatively low foxo levels and overexpressed foxo, either ubiquitously or in a tissue-specific manner. We found that ubiquitous foxo overexpression (OE) accelerated aging, induced the early onset of age-related phenotypes, increased sensitivity to thermal stress, and deregulated metabolic and proteostatic pathways; these phenotypes were more intense in transgenic flies expressing high levels of foxo. Interestingly, there is a defined dosage of foxo OE in muscles and cardiomyocytes that shifts energy resources into longevity pathways and thus ameliorates not only tissue but also organismal age-related defects. Further, we found that foxo OE stimulates in an Nrf2/cncC dependent-manner, counteracting proteostatic pathways, e.g., the ubiquitin-proteasome pathway, which is central in ameliorating the aberrant foxo OE-mediated toxicity. These findings highlight the differential dose- and tissue-dependent effects of foxo on aging, metabolic and proteostatic pathways, along with the foxo-Nrf2/cncC functional crosstalk.

Download Full-text

Sarcopenia in Autoimmune and Rheumatic Diseases: A Comprehensive Review

International Journal of Molecular Sciences ◽

10.3390/ijms21165678 ◽

2020 ◽

Vol 21 (16) ◽

pp. 5678

Author(s):

Hyo Jin An ◽

Kalthoum Tizaoui ◽

Salvatore Terrazzino ◽

Sarah Cargnin ◽

Keum Hwa Lee ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Diseases ◽

Rheumatic Diseases ◽

Autoimmune Diabetes ◽

Clinical Importance ◽

Underlying Disease ◽

Age Related ◽

Significant Disability ◽

Definition Of ◽

And Function

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.

Download Full-text

Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00489.2010 ◽

2010 ◽

Vol 299 (6) ◽

pp. R1572-R1581 ◽

Cited By ~ 68

Author(s):

Janna R. Jackson ◽

Michael J. Ryan ◽

Yanlei Hao ◽

Stephen E. Alway

Keyword(s):

Oxidative Stress ◽

Muscle Force ◽

Isometric Force ◽

Redox Status ◽

Hindlimb Suspension ◽

Muscle Disuse ◽

Old Rats ◽

Endogenous Antioxidant ◽

And Function ◽

Gastrocnemius Muscles

Hindlimb suspension (HLS) elicits muscle atrophy, oxidative stress, and apoptosis in skeletal muscle. Increases in oxidative stress can have detrimental effects on muscle mass and function, and it can potentially lead to myonuclear apoptosis. Resveratrol is a naturally occurring polyphenol possessing both antioxidant and antiaging properties. To analyze the capacity of resveratrol to attenuate oxidative stress, apoptosis and muscle force loss were measured following 14 days of HLS. Young (6 mo) and old (34 mo) rats were administered either 12.5 mg·kg−1·day−1 of trans-resveratrol, or 0.1% carboxymethylcellulose for 21 days, including 14 days of HLS. HLS induced a significant decrease in plantarflexor isometric force, but resveratrol blunted this loss in old animals. Resveratrol increased gastrocnemius catalase activity, MnSOD activity, and MnSOD protein content following HLS. Resveratrol reduced hydrogen peroxide and lipid peroxidation levels in muscles from old animals after HLS. Caspase 9 abundance was reduced and Bcl-2 was increased, but other apoptotic markers were not affected by resveratrol in the gastrocnemius muscle after HLS. The data indicate that resveratrol has a protective effect against oxidative stress and muscle force loss in old HLS animals; however, resveratrol was unable to attenuate apoptosis following HLS. These results suggest that resveratrol has the potential to be an effective therapeutic agent to treat muscle functional decrements via improving the redox status associated with disuse.

Download Full-text