Muscle fibroblasts and stem cells stimulate motor neurons in an age and exercise‐dependent manner

2024/11/18 by Casper Soendenbroe, Peter Schjerling, Cecilie J. L. Bechshøft +6 · 1 voice · 11 citations
Biochemistry, Genetics and Molecular Biology · Engineering · Medicine · Neuroscience · #Adipose Tissue and Metabolism #Biology #Cell biology #Muscle Physiology and Disorders #Muscle activation and electromyography studies #Neuroscience #Stem cell

paper · pdf · doi:10.1111/acel.14413

published in Aging Cell 24(3), e14413 (Wiley)

openalex publication_date 2024/11/18 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06

Abstract

Exercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age-related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise.

Citations

• What is the cause of the ageing atrophy?
• Lumbar Motoneurons of Man: I) Number and Diameter Histogram of Alpha and Gamma Axons of Ventral Root
• The numbers of limb motor neurons in the human lumbosacral cord throughout life
• Age-related Reduction in 8th Cervical Ventral Nerve Root Myelinated Fiber Diameters and Numbers in Man

Cited by

• Enhancing muscle and brain resilience: The role of prehabilitative exercise in mitigating disuse effects
• Insights into human muscle biology from human primary skeletal muscle cell culture
• Insights into human muscle biology from human primary skeletal muscle cell culture. [europepmc]
• Acutely denervated muscle EVs reshape neuronal mitochondrial metabolism via retrograde signaling to rescue peripheral nerve injury. [europepmc]
• Effectiveness of exercise intervention on muscle mass, muscle strength, and physical function among postmenopausal women with sarcopenia: a systematic review and meta-analysis. [europepmc]
• Muscle fibre denervation in ageing. [europepmc]
• Modulation of satellite cell function to alleviate age-related sarcopenia: Electrical stimulation & Ca²⁺ signaling combined approach. [europepmc]

Discussions

• 🤩How does exercise keep us strong? Led by Casper Soendenbroe, motor neurons are better supported by muscle stem cells and fibroblasts from life long exercisers v inactive ppl🏃 #keepmoving 🙏 @bench [bsky, 55 points, 2 comments]

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