miR-146a-5p modulates cellular senescence and apoptosis in visceral adipose tissue of long-lived Ames dwarf mice and in cultured pre-adipocytes.
Apoptosis
Cellular senescence
Pre-Adipocytes
Visceral adipose tissue
miR-146a-5p
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
02
09
2021
accepted:
09
11
2021
pubmed:
27
11
2021
medline:
15
3
2022
entrez:
26
11
2021
Statut:
ppublish
Résumé
MicroRNAs (miRNAs) are potent regulators of multiple biological processes. Previous studies have demonstrated that miR-146a-5p increases in normal mice during aging, while long-living Ames dwarf (df/df) mice maintain youthful levels of this miRNA. The aim of this study was to elucidate the involvement of miR-146a-5p in modulating cellular senescence and apoptosis in visceral adipose tissue of df/df mice and cultured pre-adipocytes. To test the effects of miR-146a-5p overexpression on visceral adipose tissue, wild-type, and df/df mice, were treated with miRNA-negative control-base and df/df were transfected with 4 or 8 µg/g of a miR-146a-5p mimetic, respectively. Effects of miR-146a-5p overexpression were also evaluated in 3T3-L1 cells cultured under high and normal glucose conditions. Treatment with miR-146a-5p mimetic increased cellular senescence and inflammation and decreased pro-apoptotic factors in visceral adipose tissue of df/df mice. The miR-146a-5p mimetic induced similar effects in 3T3-L1 cells cultivated at normal but not high glucose levels. Importantly, 3T3-L1 HG cells in high glucose conditions showed significantly higher expression of miR-146a-5p than 3T3-L1 grown in normal glucose conditions. These results indicate that miR-146a-5p can be a marker for cellular senescence. This miRNA represents one of the significant SASP factors that if not precisely regulated, can accentuate inflammatory responses and stimulate senescence in surrounding non-senescent cells. The role of miR-146a-5p is different in healthy versus stressed cells, suggesting potential effects of this miRNA depend on overall organismal health, aging, and metabolic state.
Identifiants
pubmed: 34825304
doi: 10.1007/s11357-021-00490-3
pii: 10.1007/s11357-021-00490-3
pmc: PMC8811002
doi:
Substances chimiques
MicroRNAs
0
Mirn146 microRNA, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
503-518Subventions
Organisme : NIA NIH HHS
ID : U19 AG056278
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG062985
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG061414
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG062413
Pays : United States
Organisme : NIA NIH HHS
ID : R03 AG059846
Pays : United States
Organisme : NIA NIH HHS
ID : R15 AG059190
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG013925
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG043376
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to American Aging Association.
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