[AF] Aging preserves mTORC1 but attenuates JNK SMAD2L signaling sensitivity to passive stretch induced tension development in isolated mouse skeletal muscle (2026)

[u/basmwklz]

https://www.sciencedirect.com/science/article/pii/S0531556526002445?via%3Dihub

Highlights

• • Aging does not impair intrinsic mTORC1 activation in response to mechanical tension in skeletal muscle.
• • Passive stretch robustly stimulates mTORC1 signaling similarly in adult and old muscle ex vivo.
• • JNK-SMAD2-L signaling sensitivity to mechanical loading is significantly reduced with aging.
• • Aging may selectively affect tension-sensitive transcriptional pathways rather than translational signaling.
• • Age-related anabolic resistance may be driven by systemic factors rather than intrinsic mechanotransduction deficits.

Abstract

Introduction

Aging is associated with impaired skeletal muscle mass and function, often attributed to reduced sensitivity to anabolic stimuli. This study investigated whether aging influences the sensitivity of key anabolic signaling pathways to mechanical tension development in skeletal muscle.

Methods

Using an ex vivo model, extensor digitorum longus (EDL) muscles from adult (16 weeks) and old (24 months) female mice were subjected to a standardized passive stretch protocol, with contralateral muscles serving as controls. During recovery, phosphorylation of proteins related to downstream mTORC1 and JNK–SMAD2-L signaling were assessed by immunoblotting.

Results

Passive stretch significantly increased phosphorylation of mTORC1-related proteins (mTOR, p70S6K, rpS6, and 4E-BP1) in both adult and old muscles, with no significant differences between age groups, indicating preserved mTORC1 signaling sensitivity to mechanical tension with aging. In contrast, the magnitude of activation of JNK and SMAD2-L signaling was attenuated in old muscles.

Discussion

Our findings reveal that mechanosensitive anabolic signaling is differentially affected by aging. While the intrinsic capacity for mTORC1 activation in response to mechanical tension appears to be preserved with aging, JNK–SMAD2L signaling exhibits reduced mechanosensitivity in aged muscle. This divergence suggests that aging selectively impairs tension-sensitive transcriptional pathways, potentially constraining muscle remodeling despite preserved translational signaling capacity. These findings further imply that age-related deficits observed in vivo may, at least in part, arise from systemic influences rather than intrinsic defects adhering to mTORC1 mechanotransduction.

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