Dense Body and M-Line Maintenance Underlies Age-Resistant Muscle Function

Jiang L, Wang X, Zhang D, Yee Yuen KW, Tse YC. RSU-1 regulates the integrity of dense bodies in muscle cells of aging Caenorhabditis elegans. iScience 2024;27(6):109854. doi: 10.1016/j.isci.2024.109854.

Background: Muscle contraction depends on the sarcomere, whose dense bodies and M-lines ensure force transmission during locomotion. With aging, muscle strength and structure deteriorate, contributing to sarcopenia. The conserved Ras suppressor protein RSU-1 localizes to the dense body and M-line in Caenorhabditis elegans muscle cells, yet its precise role in maintaining sarcomere integrity during aging has remained unclear.

Hypothesis: This study hypothesized that RSU-1, through its interaction with UNC-97/PINCH, is essential for preserving dense body and M-line structure and thus maintaining muscle integrity and locomotion in aging C. elegans.

Methods: The authors employed transgenic C. elegans strains expressing fluorescently tagged RSU-1 and UNC-97 to visualize their localization by high-resolution confocal microscopy. Locomotion and burrowing abilities were quantified using WormLab. Structural analyses of muscle sarcomeres were performed through phalloidin staining, immunofluorescence of myosin filaments and transmission electron microscopy.

Results: RSU-1 colocalized with UNC-97 at dense bodies and M-lines, forming donut-shaped structures. Loss of RSU-1 or disruption of its UNC-97 interaction did not affect young worms but significantly reduced locomotion and burrowing in aged worms. Aging mutants displayed disorganized actin and myosin filaments, elongated dense bodies, disrupted M-lines and fewer A-bands, demonstrating structural degeneration.

Conclusions: RSU-1 is crucial for maintaining sarcomere organization and muscle performance during aging. Its interaction with UNC-97 stabilizes dense bodies and M-lines, preventing premature sarcopenia in C. elegans.