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

Authors

Samantha L. Asche-Godin, National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
Zachary A. Graham, Research Service, Birmingham VA Medical Center, Birmingham, Alabama, USA.
Adina Israel, National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
Lauren M. Harlow, National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
Weihua Huang, Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, New York, USA.
Zhiying Wang, Bone-Muscle Research Center, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas, USA.
Marco Brotto, Bone-Muscle Research Center, College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas, USA.
Charles Mobbs, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Christopher P. Cardozo, National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
Fred C. Ko, Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Author Type(s)

Faculty

DOI

10.1093/gerona/glac043

Journal Title

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

First Page

1939

Last Page

1950

Document Type

Article

Publication Date

10-6-2022

Department

Pharmacology

Abstract

This study aimed to characterize the effects of laparotomy on postoperative physical function and skeletal muscle gene expression in male C57BL/6N mice at 3, 20, and 24 months of age to investigate late-life vulnerability and resiliency to acute surgical stress. Pre and postoperative physical functioning was assessed by forelimb grip strength on postoperative day (POD) 1 and 3 and motor coordination on POD 2 and 4. Laparotomy-induced an age-associated postoperative decline in forelimb grip strength that was the greatest in the oldest mice. While motor coordination declined with increasing age at baseline, it was unaffected by laparotomy. Baseline physical function as stratified by motor coordination performance (low functioning vs high functioning) in 24-month-old mice did not differentially affect postlaparotomy reduction in grip strength. RNA sequencing of soleus muscles showed that laparotomy-induced age-associated differential gene expression and canonical pathway activation with the greatest effects in the youngest mice. Examples of such age-associated, metabolically important pathways that were only activated in the youngest mice after laparotomy included oxidative phosphorylation and NRF2-mediated oxidative stress response. Analysis of lipid mediators in serum and gastrocnemius muscle showed alterations in profiles during aging and confirmed an association between such changes and functional status in gastrocnemius muscle. These findings demonstrate a mouse model of laparotomy which recapitulated some features of postoperative skeletal muscle decline in older adults, and identified age-associated, laparotomy-induced molecular signatures in skeletal muscles. Future research can build upon this model to study molecular mechanisms of late-life vulnerability and resiliency to acute surgical stress.

Recommended Citation

Asche-Godin, S. L., Graham, Z. A., Israel, A., Harlow, L. M., Huang, W., Wang, Z., Brotto, M., Mobbs, C., Cardozo, C. P., & Ko, F. C. (2022). RNA-Sequencing Reveals a Gene Expression Signature in Skeletal Muscle of a Mouse Model of Age-Associated Postoperative Functional Decline. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 77 (10), 1939-1950. https://doi.org/10.1093/gerona/glac043