RNA-sequencing Reveals a Gene Expression Signature in Skeletal Muscle of a Mouse Model of Age-associated Postoperative Functional Decline

Journals of Gerontology: Biological Sciences, 2022 · DOI: 10.1093/gerona/glac043 · Published: October 1, 2022

Simple Explanation

This study explores how surgery affects older adults, who often face more complications. Researchers used mice of different ages to model surgery's impact on muscle function and genes. The goal was to understand why older individuals are more vulnerable to poor surgical outcomes. The study found that surgery-induced muscle weakness was greater in older mice, mirroring what is observed in human older adults. The research also identified specific genes affected by surgery, offering clues about how aging muscles respond to surgical stress. By understanding the molecular changes in muscles after surgery, scientists hope to find ways to improve recovery and reduce complications for older surgical patients, focusing on maintaining muscle health and function.

Study Duration

Not specified

Participants

Male C57BL/6N mice at 3, 20, and 24 months of age

Evidence Level

Not specified

Key Findings

1
Laparotomy induced an age-associated postoperative decline in forelimb grip strength, with the greatest decline in the oldest mice.
2
Laparotomy-induced age-associated differential gene expression and canonical pathway activation in skeletal muscles, with the greatest effects in the youngest mice.
3
Lipidomics analysis showed alterations in lipid mediator profiles during aging and an association between these changes and functional status in gastrocnemius muscle.

Research Summary

This study characterized the effects of laparotomy on postoperative physical function and skeletal muscle gene expression in male C57BL/6N mice across life span. The study found that laparotomy-induced age-associated decline in muscle strength and differential regulation of expression of mRNAs encoding proteins participating in canonical pathways in skeletal muscles after surgery. Lipidomics studies in gastrocnemius muscles confirmed the associations between profiles of signaling lipids and age/functional status in mice.

Practical Implications

Model for Postoperative Decline

The mouse model of laparotomy recapitulates some features of postoperative skeletal muscle decline observed in older adults, providing a valuable tool for future research.

Targeted Interventions

Identifying age-associated, laparotomy-induced molecular signatures in skeletal muscles can inform the development of targeted interventions to improve surgical outcomes in older adults.

Understanding Vulnerability

Further investigation of molecular mechanisms of late-life vulnerability to acute surgical stress and resiliency to surgery-induced physical decline can lead to more effective strategies for managing surgical risks in the elderly.

Study Limitations

1
The study focused solely on male mice, and whether the laparotomy procedure has similar effects in female mice remains unknown.
2
Several muscle groups were used from each animal to limit the number of animals used in our experiments.
3
The potential impact of age-associated changes in adiposity on our findings.

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