Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The effect of calorie restriction on mouse skeletal muscle is sex, strain and time-dependent.

ABSTRACT: Loss of skeletal muscle mass and function occurs with increasing age. Calorie restriction (CR) increases the lifespan of C57Bl/6 mice, but not in the shorter-lived DBA/2 strain. There is some evidence that calorie restriction reduces or delays many of the age-related defects that occur in rodent skeletal muscle. We therefore investigated the effect of short (2.5 month) and longer term (8.5 and 18.5 months) CR on skeletal muscle in male and female C57Bl/6 and DBA/2 mice. We found that short-term CR increased the satellite cell number and collagen VI content of muscle, but resulted in a delayed regenerative response to injury.Consistent with this, the in vitro proliferation of satellite cells derived from these muscles was reduced by CR. The percentage of stromal cells, macrophages, hematopoietic stem cells and fibroadipogenic cells in the mononucleated cell population derived from skeletal muscle was reduced by CR at various stages. But overall, these changes are neither consistent over time, nor between strain and sex. The fact that changes induced by CR do not persist with time and the dissimilarities between the two mouse strains, combined with sex differences, urge caution in applying CR to improve skeletal muscle function across the lifespan in humans.

SUBMITTER: Boldrin L

PROVIDER: S-EPMC5505993 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Short-term calorie restriction enhances skeletal muscle stem cell function.

Project description:Calorie restriction (CR) extends life span and ameliorates age-related pathologies in most species studied, yet the mechanisms underlying these effects remain unclear. Using mouse skeletal muscle as a model, we show that CR acts in part by enhancing the function of tissue-specific stem cells. Even short-term CR significantly enhanced stem cell availability and activity in the muscle of young and old animals, in concert with an increase in mitochondrial abundance and induction of conserved metabolic and longevity regulators. Moreover, CR enhanced endogenous muscle repair and CR initiated in either donor or recipient animals improved the contribution of donor cells to regenerating muscle after transplant. These studies indicate that metabolic factors play a critical role in regulating stem cell function and that this regulation can influence the efficacy of recovery from injury and the engraftment of transplanted cells.

| S-EPMC3561899 | biostudies-literature

Preventing the calorie restriction-induced increase in insulin-stimulated Akt2 phosphorylation eliminates calorie restriction's effect on glucose uptake in skeletal muscle.

Project description:Calorie restriction (CR; ~60% of ad libitum, AL, consumption) improves insulin-stimulated glucose uptake in skeletal muscle. The precise cellular mechanism for this healthful outcome is unknown, but it is accompanied by enhanced insulin-stimulated activation of Akt. Previous research using Akt2-null mice demonstrated that Akt2 is essential for the full CR-effect on insulin-stimulated glucose uptake by muscle. However, because Akt2-null mice were completely deficient in Akt2 in every cell throughout life, it would be valuable to assess the efficacy of transient, muscle-specific Akt inhibition for attenuation of CR-effects on glucose uptake. Accordingly, we used a selective Akt inhibitor (MK-2206) to eliminate the CR-induced elevation in insulin-stimulated Akt2 phosphorylation and determined the effects on Akt substrates and glucose uptake. We incubated isolated epitrochlearis muscles from 9-month-old AL and CR (~60-65% of AL intake for 6months) rats with or without MK-2206 and measured insulin-stimulated (1.2nM) glucose uptake and phosphorylation of the insulin receptor (Tyr1162/1163), pan-Akt (Thr308 and Ser473), Akt2 (Thr308 and Ser473), AS160/TBC1D4 (Thr642), and Filamin C (Ser2213). Incubation of isolated skeletal muscles with a dose of a selective Akt inhibitor that eliminated the CR-induced increases in Akt2 phosphorylation prevented CR's effects on insulin-stimulated glucose uptake, pAS160(Thr642) and pFilamin C(Ser2213) without altering pIR(Tyr1162/1163). These data provide compelling new evidence linking the CR-induced increase in insulin-stimulated Akt2 phosphorylation to CR's effects on insulin-mediated phosphorylation of Akt substrates and glucose uptake in skeletal muscle.

| S-EPMC3444632 | biostudies-literature

Loss of AMP-activated protein kinase-?2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle.

Project description:Whether the well-known metabolic switch AMP-activated protein kinase (AMPK) is involved in the insulin-sensitizing effect of calorie restriction (CR) is unclear. In this study, we investigated the role of AMPK in the insulin-sensitizing effect of CR in skeletal muscle. Wild-type (WT) and AMPK-?2(-/-) mice received ad libitum (AL) or CR (8 weeks at 60% of AL) feeding. CR increased the protein level of AMPK-?2 and phosphorylation of AMPK-?2. In WT and AMPK-?2(-/-) mice, CR induced comparable changes of body weight, fat pad weight, serum triglycerides, serum nonesterified fatty acids, and serum leptin levels. However, decreasing levels of fasting/fed insulin and fed glucose were observed in WT mice but not in AMPK-?2(-/-) mice. Moreover, CR-induced improvements of whole-body insulin sensitivity (evidenced by glucose tolerance test/insulin tolerance test assays) and glucose uptake in skeletal muscle tissues were abolished in AMPK-?2(-/-) mice. Furthermore, CR-induced activation of Akt-TBC1D1/TBC1D4 signaling, inhibition of mammalian target of rapamycin-S6K1-insulin receptor substrate-1 pathway, and induction of nicotinamide phosphoribosyltransferase-NAD(+)-sirtuin-1 cascade were remarkably impaired in AMPK-?2(-/-) mice. CR serum increased stability of AMPK-?2 protein via inhibiting the X chromosome-linked ubiquitin-specific protease 9-mediated ubiquitylation of AMPK-?2. Our results suggest that AMPK may be modulated by CR in a ubiquitylation-dependent manner and acts as a chief dictator for the insulin-sensitizing effects of CR in skeletal muscle.

| S-EPMC3331748 | biostudies-literature

Mouse cerebellum LC-MSMS: effect of calorie restriction

Project description:The cerebellum harbors a circadian clock that can be shifted by scheduled mealtime and participates in behavioral anticipation of food access. To determine which cerebellar proteins are modified by time-of-day and/or feeding time, we determined day-night variations of proteome in the cerebellum of mice fed either ad libitum or only during daytime (from noon to lights off). Two-dimensional differences in gel electrophoresis (2D-DIGE) combined with two-way analyses of variance reveals that a majority of cerebellar proteins are significantly regulated by feeding conditions (food availability). Levels of few other cerebellar proteins were modulated exclusively by daily (or circadian) cues, independent of meal time, and others due to combined influence of meal time and time-of-day. Changes reflect behavioral anticipation of mealtime and/or feeding-induced shift in the circadian clock of the cerebellum.

2021-04-06 | PXD021056 | Pride

mRNA-Seq reveals complex patterns of gene regulation and expression in the mouse skeletal muscle transcriptome associated with calorie restriction.

Project description:Sarcopenia is an age-associated loss of skeletal muscle mass and strength that increases the risk of disability. Calorie restriction (CR), the consumption of fewer calories while maintaining adequate nutrition, mitigates sarcopenia and many other age-related diseases. To identify potential mechanisms by which CR preserves skeletal muscle integrity during aging, we used mRNA-Seq for deep characterization of gene regulation and mRNA abundance in skeletal muscle of old mice compared with old mice subjected to CR. mRNA-Seq revealed complex CR-associated changes in expression of mRNA isoforms, many of which occur without a change in total message abundance and thus would not be detected by methods other than mRNA-Seq. Functional annotation of differentially expressed genes reveals CR-associated upregulation of pathways involved in energy metabolism and lipid biosynthesis, and downregulation of pathways mediating protein breakdown and oxidative stress, consistent with earlier microarray-based studies. CR-associated changes not noted in previous studies involved downregulation of genes controlling actin cytoskeletal structures and muscle development. These CR-associated changes reflect generally healthier muscle, consistent with CR's mitigation of sarcopenia. mRNA-Seq generates a rich picture of the changes in gene expression associated with CR, and may facilitate identification of genes that are primary mediators of CR's effects.

| S-EPMC3327143 | biostudies-literature

Identification of novel genes associated with exercise and calorie restriction effects in skeletal muscle.

Project description:Exercise and caloric restriction (CR) significantly increase longevity across a range of species and delay aging-related losses in organ function. Although both interventions enhance skeletal muscle function, the molecular mechanisms underlying these associations are unknown. We sought to identify genes regulated by CR and exercise in muscle, and investigate their relationship with muscle function. To do this, expression profiles of Gene Expression Omnibus datasets obtained from the muscle tissue of calorie-restricted male primates and young men post-exercise were analyzed. There were seven transcripts (ADAMTS1, CPEB4, EGR2, IRS2, NR4A1, PYGO1, and ZBTB43) that were consistently upregulated by both CR and exercise training. We used C2C12 murine myoblasts to investigate the effect of silencing these genes on myogenesis, mitochondrial respiration, autophagy, and insulin signaling, all of which are processes affected by CR and exercise. Our results show that in C2C12 cells, Irs2 and Nr4a1 expression were critical for myogenesis, and five genes (Egr2, Irs2, Nr4a1, Pygo1, and ZBTB43) regulated mitochondrial respiration while having no effect on autophagy. Cpeb4 knockdown increased the expression of genes involved in muscle atrophy and induced myotube atrophy. These findings suggest new resources for studying the mechanisms underlying the beneficial effects of exercise and calorie restriction on skeletal muscle function and lifespan extension.

| S-EPMC10292903 | biostudies-literature

Calorie restriction effects on circadian rhythms in gene expression are sex dependent.

Project description:The rhythms in the expression of circadian clock genes are affected by calorie restriction (CR), a dietary paradigm known to increase lifespan. Many physiological effects of CR differ between males and females; here we investigated if the sex of animals affects the CR induced changes in the circadian rhythms. The liver expression of some circadian clock genes such as Bmal1 and three Periods (Per1, Per2 and Per3) and the effect of CR on the expression of these genes were sex independent, while the expression of Rev-Erb alpha, Ror gamma and both Cryptochome (Cry1 and Cry2) genes was different between males and females. The effect of CR on Rev-Erb alpha, Ror gamma and Cry1 gene expression was sex dependent. The expression and the effects of CR were sex-specific for several genes previously reported to be regulated by CR: Fmo3, Mup4, Serpina12 and Cyp4a12, while the expression of Cyp4a14a was sex independent. IGF signaling plays an important role in aging and CR effects. Igf-1 expression is regulated by CR and by the circadian clock, we found that rhythms in Igf-1 expression have sexual dimorphism. Our data provide molecular evidence that the sex of animals is an important modulator of circadian rhythms in gene expression and their response to CR.

| S-EPMC5575277 | biostudies-literature

The consequences of a high-calorie diet background before calorie restriction on skeletal muscles in a mouse model.

Project description:The beneficial effects of calorie restriction (CR) are numerous. However, there is no scientific evidence about how a high-calorie diet (HCD) background influences the mechanisms underlying CR on skeletal muscles in an experimental mouse model. Herein we present empirical evidence showing significant interactions between HCD (4 months) and CR (3 months). Pectoralis major and quadriceps femoris vastus medialis, in the experimental and control groups, displayed metabolic and physiologic heterogeneity and remarkable plasticity, according to the dietary interventions. HCD-CR not only altered genetic activation patterns of satellite SC markers but also boosted the expression of myogenic regulatory factors and key activators of mitochondrial biogenesis, which in turn were also associated with metabolic fiber transition. Our data prompt us to theorize that the effects of CR may vary according to the physiologic, metabolic, and genetic peculiarities of the skeletal muscle described here and that INTM/IM lipid infiltration and tissue-specific fuel-energy status (demand/supply) both hold dependent-interacting roles with other key anti-aging mechanisms triggered by CR. Systematic integration of an HCD with CR appears to bring potential benefits for skeletal muscle function and energy metabolism. However, at this stage of our research, an optimal balance between the two dietary conditions, where anti-aging effects can be accomplished, is under intensive investigation in combination with other tissues and organs at different levels of organization within the organ system.

| S-EPMC8266348 | biostudies-literature

Effect of age, calorie restriction and resveratrol on gene expression in mouse heart, brain, and skeletal muscle

Project description:Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR. Keywords: aging intervention study

2008-06-10 | GSE11291 | GEO

The Impact of Aging, Calorie Restriction and Dietary Fat on Autophagy Markers and Mitochondrial Ultrastructure and Dynamics in Mouse Skeletal Muscle.

Project description:Loss of skeletal muscle mass and function is a hallmark of aging. This phenomenon has been related to a dysregulation of mitochondrial function and proteostasis. Calorie restriction (CR) has been demonstrated to delay aging and preserve function until late in life, particularly in muscle. Recently, we reported the type of dietary fat plays an important role in determining life span extension with 40% CR in male mice. In these conditions, lard fed mice showed an increased longevity compared to mice fed soybean or fish oils. In this article, we analyze the effect of 40% CR on muscle mitochondrial mass, autophagy, and mitochondrial dynamics markers in mice fed these diets. In CR fed animals, lard preserved muscle fibers structure, mitochondrial ultrastructure, and fission/fusion dynamics and autophagy, not only compared to control animals, but also compared with CR mice fed soybean and fish oils as dietary fat. We focus our discussion on dietary fatty acid saturation degree as an essential predictor of life span extension in CR mice.

| S-EPMC6521922 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data