Dataset Information

Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.

ABSTRACT: The elderly often suffer from progressive muscle weakness and regenerative failure. We demonstrate that muscle regeneration is impaired with aging owing in part to a cell-autonomous functional decline in skeletal muscle stem cells (MuSCs). Two-thirds of MuSCs from aged mice are intrinsically defective relative to MuSCs from young mice, with reduced capacity to repair myofibers and repopulate the stem cell reservoir in vivo following transplantation. This deficiency is correlated with a higher incidence of cells that express senescence markers and is due to elevated activity of the p38? and p38? mitogen-activated kinase pathway. We show that these limitations cannot be overcome by transplantation into the microenvironment of young recipient muscles. In contrast, subjecting the MuSC population from aged mice to transient inhibition of p38? and p38? in conjunction with culture on soft hydrogel substrates rapidly expands the residual functional MuSC population from aged mice, rejuvenating its potential for regeneration and serial transplantation as well as strengthening of damaged muscles of aged mice. These findings reveal a synergy between biophysical and biochemical cues that provides a paradigm for a localized autologous muscle stem cell therapy for the elderly.

SUBMITTER: Cosgrove BD

PROVIDER: S-EPMC3949152 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.

Cosgrove Benjamin D BD Gilbert Penney M PM Porpiglia Ermelinda E Mourkioti Foteini F Lee Steven P SP Corbel Stephane Y SY Llewellyn Michael E ME Delp Scott L SL Blau Helen M HM

Nature medicine 20140216 3

The elderly often suffer from progressive muscle weakness and regenerative failure. We demonstrate that muscle regeneration is impaired with aging owing in part to a cell-autonomous functional decline in skeletal muscle stem cells (MuSCs). Two-thirds of MuSCs from aged mice are intrinsically defective relative to MuSCs from young mice, with reduced capacity to repair myofibers and repopulate the stem cell reservoir in vivo following transplantation. This deficiency is correlated with a higher in ...[more]

PMID: 24531378

Similar Datasets

Project description:BackgroundLittle is known about the response of the equine respiratory muscles to training.ObjectivesTo measure an index of inspiratory muscle strength (IMSi) before and after a period of conventional exercise training (phase 1) and inspiratory muscle training (IMT), comparing high-load (treatment) and low-load (control) groups (phase 2).Study designProspective randomised controlled trial.MethodsPhase 1: Twenty National Hunt Thoroughbred racehorses performed an inspiratory muscle strength test (IMST) twice on two occasions; when unfit at timepoint A (July), and when race fit at timepoint B (October). Phase 2: Thirty-five Thoroughbred racehorses at race fitness were randomly assigned into a high-load (treatment, n = 20) or low-load (control, n = 15) IMT group. The high-load group followed an IMT protocol that gradually increased the inspiratory pressure applied every 4 days. The low-load group underwent sham IMT with a low training load. The IMT was performed 5 days/week for 10 weeks. The IMST was performed twice on two occasions, timepoint B (October) and timepoint C (January). Conventional exercise training and racing continued during the study period. The peak IMSi values obtained from the different groups at timepoints A, B and C were compared using a Wilcoxon Signed Rank Test.ResultsPhase 1: There was a significant increase in IMSi from timepoint A: 22.5 cmH2 O (21-25) to timepoint B: 26 cmH2 O (24-30) (p = 0.015). Phase 2: From timepoint B to C there was a significant increase in IMSi for the high-load group 34 cmH2 O (28-36) (p = 0.001) but not the low-load group 26 cmH2 O (24-30) (p = 0.929). The peak IMSi at timepoint C was significantly higher for the high-load than low-load group (p = 0.019).Main limitationsSingle centre study with only National Hunt horses undergoing race-training included.ConclusionsIn horses undergoing race training there is a significant increase in IMSi in response to conventional exercise training and high-load IMT.

Dataset Information

Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.

Publications

Rejuvenation of the muscle stem cell population restores strength to injured aged muscles.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets