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

Author:

Asche-Godin Samantha L12ORCID,Graham Zachary A34,Israel Adina1,Harlow Lauren M1,Huang Weihua5,Wang Zhiying6,Brotto Marco6,Mobbs Charles78,Cardozo Christopher P12,Ko Fred C89

Affiliation:

1. National Center for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center , Bronx, New York , USA

2. Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, New York , USA

3. Research Service, Birmingham VA Medical Center , Birmingham, Alabama , USA

4. Department of Cell, Developmental, and Integrative Biology, University of Alabama-Birmingham , Birmingham , USA

5. Department of Pathology, Microbiology and Immunology, New York Medical College , Valhalla, New York , USA

6. Bone-Muscle Research Center, College of Nursing and Health Innovation, University of Texas at Arlington , Arlington, Texas , USA

7. Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, New York , USA

8. Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai , New York, New York , USA

9. Geriatric Research Education and Clinical Center, James J. Peters VA Medical Center , Bronx, New York , USA

Abstract

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.

Funder

National Institute on Aging

VA Rehabilitation and Development Service

National Institutes of Health

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Neurological Disorders and Stroke

Publisher

Oxford University Press (OUP)

Subject

Geriatrics and Gerontology,Aging

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