The impact of sarcolipin ablation on calcineurin signalling and muscle phenotype with aging
Notice bibliographique
Résumé
Sarcolipin (SLN), a small protein inhibitor of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), is dynamically upregulated in atrophic unloading and disease states where it promotes muscle health by activating calcineurin (Cn) and the dephosphorylation and subsequent nuclear translocation of nuclear factor of activated T-cells (NFAT). This study sought to examine how the ablation of SLN impacted Cn signalling, fibre type profile and muscle mass in both male and female mice with aging. Male and female, wild type (WT) and SLN knockout (SLNKO) mice were assessed at two age groups (young adult (4-6M) and older adult (18+M)) for muscle mass (soleus:body weight ratio, fibre type specific cross-sectional area), fibre type profile and protein expression (SLN, Cn, and NFAT). SLN content was significantly greater in WT females (p <00.1) and older animals (5<0.05) and absent from SLNKO. As SLN has been linked to Cn signalling previously, we hypothesized that the increased SLN content in female and aged animals may promote Cn signalling. While there was a trend for lower Cn expression with aging (p=0.10), neither sex nor genotype significantly impacted Cn expression. To examine activation of Cn, the ratio of inactive phosphorylated NFAT to total NFAT was assessed via Western Blotting. We found that aging significantly increased the activation of Cn (p<0.01) and there was a trend (p=0.10) towards greater NFATp/NFAT with SLN ablation signifying a reduction in Cn signalling. As Cn is a known regulator of muscle fibre type, we examined fibre type profile using immunofluorescence and found aging increased the percentage of type I fibres (p<0.001), which was witnessed more predominately in female mice regardless of genotype. Furthermore, when examining type II fibres, we found a significant sex by age interaction (p<0.05) in which both WT and SLNKO females displayed reduced type II fibres with aging while males did not display this apparent shift. With respect to muscle mass, aging, regardless of sex or genotype, was shown to significantly reduce relative muscle mass (p<0.001), however no significant reductions were found in total fibre count, or cross-sectional area of Type I or Type II fibres. In summary, this study found that WT female and aged animals display increased SLN content. Aligning with our hypothesis, there was a trend towards lower Cn signalling with SLN ablation, regardless of age or sex. However, this does not seem to be linked to changes in muscle fibre type or muscle mass, as SLNKO animals did not display significant differences from their WT counterparts. Further studies should seek to examine the role of SLN in both sex and aging further, with special focus on metabolic energy expenditure and SERCA protection. NSERC This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».