Sarcopenia is a common disorder that leads to a progressive decrease in skeletal muscle function in elderly people. Exercise effectively prevents or delays the onset and progression of sarcopenia. ...However, the molecular mechanisms underlying how exercise intervention improves skeletal muscle atrophy remain unclear. In this study, we found that 21‐month‐old zebrafish had a decreased swimming ability, reduced muscle fibre cross‐sectional area, unbalanced protein synthesis, and degradation, increased oxidative stress, and mitochondrial dysfunction, which suggests zebrafish are a valuable model for sarcopenia. Eight weeks of exercise intervention attenuated these pathological changes in sarcopenia zebrafish. Moreover, the effects of exercise on mitochondrial dysfunction were associated with the activation of the AMPK/SIRT1/PGC‐1α axis and 15‐PGDH downregulation. Our results reveal potential therapeutic targets and indicators to treat age‐related sarcopenia using exercise intervention.
Exercise reduce zebrafish sarcopenia may by activating the AMPK/SIRT1/PGC‐1α axis and down‐regulating 15‐PGDH to improve mitochondrial function. Aging induces oxidative stress and mitochondrial dysfunction in skeletal muscle, reducing myofibre cross‐sectional area, imbalance in protein synthesis and degradation, and, ultimately, muscle atrophy. Exercise inhibited oxidative stress and improved mitochondrial function may via AMPK/SIRT1/PGC‐1α axis activation and 15‐PGDH downregulation, effectively preventing age‐related sarcopenia (Created with BioRender.com.).
The Popeye domain‐containing protein 3 (POPDC3), a transmembrane protein with a unique cyclic adenosine monophosphate (cAMP) binding site, is widely expressed in mammalian tissues, with the highest ...levels of expression in skeletal muscle. POPDC3 plays a key role in many physiological and pathological processes and is considered a candidate biomarker and potential therapeutic target of cancer. In addition, POPDC3 gene variants have been associated with limb‐girdle muscular dystrophy (LGMD) type 26. However, there are only a few studies on the biological role of POPDC3, interacting proteins, potential downstream targets, and regulated signaling pathways. Therefore, this review focuses on the structure of POPDC3 protein, interacting molecules, and the role and mechanism in cancer, and in cardiac and skeletal muscle, and to review the current research progress of POPDC3 and propose possible future study directions.
POPDC3, a transmembrane protein with a cAMP‐binding site, is down‐regulated in intestinal metaplasia and gastric cancer and gastric cancer and elevated in breast and head and neck squamous cell carcinoma, and is considered a candidate biomarker and a potential therapeutic target of cancer. In addition, POPDC3 variants or homozygous missense lead to LGMD26, and whether it is associated with heart disease needs further confirmation (Created with BioRender.com).
Obesity is a highly prevalent disease that can induce metabolic syndrome and is associated with a greater risk of muscular atrophy. Mitochondria play central roles in regulating the physiological ...metabolism of skeletal muscle; however, whether a decreased mitochondrial function is associated with impaired muscle function is unclear. In this study, we evaluated the effects of a high-fat diet on muscle mitochondrial function in a zebrafish model of sarcopenic obesity (SOB). In SOB zebrafish, a significant decrease in exercise capacity and skeletal muscle fiber cross-sectional area was detected, accompanied by high expression of the atrophy-related markers Atrogin-1 and muscle RING-finger protein-1. Zebrafish with SOB exhibited inhibition of mitochondrial biogenesis and fatty acid oxidation as well as disruption of mitochondrial fusion and fission in atrophic muscle. Thus, our findings showed that muscle atrophy was associated with SOB-induced mitochondrial dysfunction. Overall, these results showed that the SOB zebrafish model established in this study may provide new insights into the development of therapeutic strategies to manage mitochondria-related muscular atrophy.
Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in ...various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle.
Diagram of the mechanism by which aerobic exercise resists sarcopenia via the miR-128/IGF1 signaling pathway. Display omitted
•D-gal immersion induces senescence and, consequently, sarcopenia in zebrafish.•Regular aerobic exercise can effectively combat the process of sarcopenia.•Mitochondrial homeostasis is improved via the miR-128/IGF-1 signaling pathway.
Recent reports indicate that mitochondrial quality decreases during non-alcoholic fatty liver disease (NAFLD) progression, and targeting the mitochondria may be a possible treatment for NAFLD. ...Exercise can effectively slow NAFLD progression or treat NAFLD. However, the effect of exercise on mitochondrial quality in NAFLD has not yet been established.
In the present study, we fed zebrafish a high-fat diet to model NAFLD, and subjected the zebrafish to swimming exercise.
After 12 weeks, swimming exercise significantly reduced high-fat diet-induced liver injury, and reduced inflammation and fibrosis markers. Swimming exercise improved mitochondrial morphology and dynamics, inducing upregulation of optic atrophy 1(OPA1), dynamin related protein 1 (DRP1), and mitofusin 2 (MFN2) protein expression. Swimming exercise also activated mitochondrial biogenesis via the sirtuin 1 (SIRT1)/ AMP-activated protein kinase (AMPK)/ PPARgamma coactivator 1 alpha (PGC1α) pathway, and improved the mRNA expression of genes related to mitochondrial fatty acid oxidation and oxidative phosphorylation. Furthermore, we find that mitophagy was suppressed in NAFLD zebrafish liver with the decreased numbers of mitophagosomes, the inhibition of PTEN-induced kinase 1 (PINK1) - parkin RBR E3 ubiquitin protein ligase (PARKIN) pathway and upregulation of sequestosome 1 (P62) expression. Notably, swimming exercise partially recovered number of mitophagosomes, which was associated with upregulated PARKIN expression and decreased p62 expression.
These results demonstrate that swimming exercise could alleviate the effects of NAFLD on the mitochondria, suggesting that exercise may be beneficial for treating NAFLD.
Long-term imbalance between fatigue and recovery may eventually lead to muscle weakness or even atrophy. We previously reported that excessive exercise induces pathological cardiac hypertrophy. ...However, the effect of excessive exercise on the skeletal muscles remains unclear. In the present study, we successfully established an excessive-exercise-induced skeletal muscle atrophy zebrafish model, with decreased muscle fiber size, critical swimming speed, and maximal oxygen consumption. High-throughput RNA-seq analysis identified differentially expressed genes in the model system compared with control zebrafish. Gene ontology and KEGG enrichment analysis revealed that the upregulated genes were enriched in autophagy, homeostasis, circadian rhythm, response to oxidative stress, apoptosis, the p53 signaling pathway, and the FoxO signaling pathway. Protein–protein interaction network analysis identified several hub genes, including keap1b, per3, ulk1b, socs2, esrp1, bcl2l1, hsp70, igf2r, mdm2, rab18a, col1a1a, fn1a, ppih, tpx2, uba5, nhlrc2, mcm4, tac1, b3gat3, and ddost, that correlate with the pathogenesis of skeletal muscle atrophy induced by excessive exercise. The underlying regulatory pathways and muscle-pressure-response-related genes identified in the present study will provide valuable insights for prescribing safe and accurate exercise programs for athletes and the supervision and clinical treatment of muscle atrophy induced by excessive exercise.
•15-PGDH degrades PGs to attenuate PG-mediated signaling and activity.•15-PGDH suppresses tumor progression and development through its targeting of PGs.•15-PGDG is a marker and potential therapeutic ...target for aging-associated diseases.
15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by HPGD) is ubiquitously expressed in mammalian tissues and catalyzes the degradation of prostaglandins (PGs; mainly PGE2, PGD2, and PGF2α) in a process mediated by solute carrier organic anion transport protein family member 2A1 (SLCO2A1; also known as PGT, OATP2A1, PHOAR2, or SLC21A2). As a key enzyme, 15-PGDH catalyzes the rapid oxidation of 15-hydroxy-PGs into 15-keto-PGs with lower biological activity. Increasing evidence suggests that 15-PGDH plays a key role in many physiological and pathological processes in mammals and is considered a potential pharmacological target for preventing organ damage, promoting bone marrow graft recovery, and enhancing tissue regeneration. Additionally, results of whole-exome analyses suggest that recessive inheritance of an HPGD mutation is associated with idiopathic hypertrophic osteoarthropathy. Interestingly, as a tumor suppressor, 15-PGDH inhibits proliferation and induces the differentiation of cancer cells (including those associated with colorectal, lung, and breast cancers). Furthermore, a recent study identified 15-PGDH as a marker of aging tissue and a potential novel therapeutic target for resisting the complex pathology of aging-associated diseases. Here, we review and summarise recent information on the molecular functions of 15-PGDH and discuss its pathophysiological implications.
This study explored the association between peripheral blood oxytocin (OT) and social anxiety disorder (SAD) and cue-induced cravings in female heroin addicts. The effect of exercise on alleviation ...of SAD and OT levels was also explored.
A total of 72 females with heroin dependence were assigned to three groups based on SAD severity. The three groups were Non-SAD control, SAD control, and SAD exercise groups. Subjects in the SAD exercise group underwent aerobic exercise and resistance training for 8 weeks (60 min/day, 5 days/week). Enzyme-linked immunosorbent assay analysis and Liebowitz Social Anxiety Scale (LSAS) scores were used to determine plasma OT concentration and SAD, respectively. Cue-induced craving was assessed using Visual Analog Scale (VAS) and Desires for Drug Questionnaire (DDQ). Mixed-effect analysis of variance and Pearson correlation analysis were used to explore the effect and correlation between different parameters.
OT levels in the SAD exercise group were significantly high after exercise (
< 0.01). LSAS, VAS, and DDQ ("Desire and Intention" and "Negative reinforcement") scores in the SAD exercise group were significantly lower after exercise (
< 0.01). Plasma OT level was negatively correlated with LSAS score (
= -0.534,
< 0.001), VAS score (
= -0.609,
< 0.001), "Desire and Intention" score (
= -0.555,
< 0.001), and "Negative reinforcement" score (
= -0.332,
< 0.01) and positively correlated with the "control" score (
= 0.258,
< 0.05). LSAS was positively correlated with VAS score (
= 0.588,
< 0.001) and "Desire and Intention" score (
= 0.282,
< 0.05).
The findings of the present study indicate that plasma OT is a potential peripheral biomarker for prediction of the severity of social anxiety in female heroin withdrawal patients. Aerobic exercise combined with resistance training plus incremental load for 8 weeks can increase plasma OT levels and significantly reduce severity of SAD and cue-induced cravings in female heroin addicts.
Members of the genus
Marinomonas
are known for their environmental adaptation and metabolically versatility, with abundant proteins associated with antifreeze, osmotic pressure resistance, ...carbohydrase and multiple secondary metabolites. Comparative genomic analysis focusing on secondary metabolites and orthologue proteins was conducted with 30 reference genome sequences in the genus
Marinomonas
. In this study, a Gram-stain-negative, rod-shaped, non-flagellated and strictly aerobic bacterium, designated as strain E8
T
, was isolated from the red algae (
Gelidium amansii
) in the coastal of Weihai, China. Optimal growth of the strain E8
T
was observed at temperatures 25–30 °C, pH 6.5–8.0 and 1–3% (w/v) NaCl. The DNA G + C content was 42.8 mol%. The predominant isoprenoid quinone was Q-8 and the major fatty acids were C
16:0
, summed feature 3 and summed feature 8. The major polar lipids were phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). Based on data obtained from this polyphasic taxonomic study, strain E8
T
should be considered as a novel species of the genus
Marinomonas
, for which the name
Marinomonas algarum
is proposed. The type strain is E8
T
(= KCTC 92201
T
= MCCC 1K07070
T
).
Li
2
Fe
0.5
Mn
0.5
SiO
4
material was synthesized by a citric acid-assisted sol-gel method. The influence of the stoichiometric ratio value of
n
(citric acid) to
n
(Fe
2+
-Mn
2+
) on the ...electrochemical properties of Li
2
Fe
0.5
Mn
0.5
SiO
4
was studied. The final sample was identified as Li
2
Fe
0.5
Mn
0.5
SiO
4
with a
P
mn2
1
monoclinic structure by X-ray diffraction analysis. The crystal phases components and crystal phase structure of the Li
2
Fe
0.5
Mn
0.4
SiO
4
material were improved as the increase of the stoichiometric ratio value of
n
(citric acid) to
n
(Fe
2+
-Mn
2+
). Field-emission scanning electron microscopy verified that the Li
2
Fe
0.5
Mn
0.5
SiO
4
particles are agglomerates of Li
2
Fe
0.5
Mn
0.5
SiO
4
primary particles with a geometric mean diameter of 220 nm. The Li
2
Fe
0.5
Mn
0.5
SiO
4
sample was used as an electrode material for rechargeable lithium ion batteries, and the electrochemical measurements were carried out at room temperature. The Li
2
Fe
0.5
Mn
0.5
SiO
4
electrode delivered a first discharge capacity of 230.1 mAh/g at the current density of 10 mA/g in first cycle and about 162 mAh/g after 20 cycles at the current density of 20 mA/g.
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