Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice.

Li F, Zhang F, Shi H, Xia H, Wei X, Liu S, Wu T, Li Y, Shu F, Chen M, Li J, Duan R

Journal of cachexia, sarcopenia and muscle26 Jun 2024Cited by 16 (Europe PMC)

PMID38925632PMCIDPMC11446704DOI10.1002/jcsm.13526PepBankPUB-38925632

Summary

BackgroundAging negatively impacts tissue repair, particularly in skeletal muscle, where the regenerative capacity of muscle stem cells (MuSCs) diminishes with age. Although aerobic exercise is known to attenuate skeletal muscle atrophy, its specific impact on the regenerative and repair capacity of MuSCs remains unclear.MethodsMice underwent moderate-intensity continuous training (MICT) from 9 months (aged + Ex-9M) or 20 months (aged + Ex-20M) to 25 months, with age-matched (aged) and adult controls. Histological examinations and MuSC transplantation assays assessed aerobic exercise effects on MuSC function and muscle regeneration. CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored.ResultsAged mice displayed significantly reduced running duration (65.33 ± 4.32 vs. 161.9 ± 1.29 min, mean ± SD, P 2), while adult, aged + Ex-9M and aged + Ex-20M groups showed significantly higher CNF counts (610.82 ± 46.76, 513.42 ± 47.19 and 548.29 ± 71.82/mm², respectively; P 2, P 2. Lenti-CCN2 MuSCs also increased fibroblast proliferation and exacerbated skeletal muscle fibrosis, while knockdown of CCN2 in aged MuSCs mitigated this pattern. AICAR supplementation, mimicking exercise, replicated the beneficial effects of aerobic exercise by mitigating muscle weight decline, enhancing satellite cell activity and reducing fibrosis.ConclusionsAerobic exercise effectively reverses the decline in endurance capacity and mitigates muscle atrophy in aged mice. It inhibits CCN2 secretion from senescent MuSCs, thereby enhancing skeletal muscle regeneration and preventing fibrosis in aged mice. AICAR supplementation mimics the beneficial effects of aerobic exercise.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In aged mice, AICAR supplementation mitigated muscle weight decline.
In plain wordsIn aged mice, AICAR reduced muscle weight loss.
Peptide
AICAR (acadesine)
Outcome
DecreaseMuscle weight decline
Study
mousen: not reported in source
Aged mice
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
AICAR supplementation, mimicking exercise, replicated the beneficial effects of aerobic exercise by mitigating muscle weight decline, enhancing satellite cell activity and reducing fibrosis.
1 context sentence(design, population, supporting numbers)
Summary · context
CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored.
Show in the study text Report a problemFND-3892563201
02AnimalAnimal study (in vivo)Efficacy outcome
In aged mice, AICAR supplementation enhanced satellite cell activity.
In plain wordsIn aged mice, AICAR increased muscle satellite cell activity.
Peptide
AICAR (acadesine)
Outcome
IncreaseSatellite cell activity
Study
mousen: not reported in source
Aged mice
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
AICAR supplementation, mimicking exercise, replicated the beneficial effects of aerobic exercise by mitigating muscle weight decline, enhancing satellite cell activity and reducing fibrosis.
1 context sentence(design, population, supporting numbers)
Summary · context
CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored.
Show in the study text Report a problemFND-3892563202
03AnimalAnimal study (in vivo)Efficacy outcome
In aged mice, AICAR supplementation reduced fibrosis.
In plain wordsIn aged mice, AICAR reduced muscle scarring.
Peptide
AICAR (acadesine)
Outcome
DecreaseMuscle fibrosis
Study
mousen: not reported in source
Aged mice
Outcome group
Muscle injury and repair · Musculoskeletal
Studied dose
Dose not stated
Source sentences
Summary
AICAR supplementation, mimicking exercise, replicated the beneficial effects of aerobic exercise by mitigating muscle weight decline, enhancing satellite cell activity and reducing fibrosis.
1 context sentence(design, population, supporting numbers)
Summary · context
CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored.
Show in the study text Report a problemFND-3892563203

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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