RNA-sequencing Reveals a Gene Expression Signature in Skeletal Muscle of a Mouse Model of Age-associated Postoperative Functional Decline.
Laparotomy
Oxidative phosphorylation
Resiliency
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
06 10 2022
06 10 2022
Historique:
received:
27
09
2021
pubmed:
17
2
2022
medline:
12
10
2022
entrez:
16
2
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35172336
pii: 6529713
doi: 10.1093/gerona/glac043
pmc: PMC9536457
doi:
Substances chimiques
Lipids
0
NF-E2-Related Factor 2
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1939-1950Subventions
Organisme : NIA NIH HHS
ID : R01 AG060341
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG039355
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119066
Pays : United States
Organisme : VA Rehabilitation and Development Service
ID : #B2020-C
Organisme : NIA NIH HHS
ID : 5K08AG050808-05
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS105621
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056504
Pays : United States
Informations de copyright
Published by Oxford University Press on behalf of The Gerontological Society of America 2022.
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