miR-146a-5p modulates cellular senescence and apoptosis in visceral adipose tissue of long-lived Ames dwarf mice and in cultured pre-adipocytes

Allancer D.C. Nunes, Moritz Weigl, Augusto Schneider, Sarah Noureddine, Lin Yu, Collin Lahde, Tatiana Dandolini Saccon, Kunal Mitra, Esther Beltran, Johannes Grillari, James L. Kirkland, Tamara Tchkonia, Paul D. Robbins, Michal M. Masternak

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)503-518
Number of pages16
JournalGeroScience
Volume44
Issue number1
DOIs
StatePublished - Feb 2022

Bibliographical note

Funding Information:
This work was supported by NIH grants R56 AG061414 (M.M.), R15 AG059190 (M.M), R03 AG059846 (M.M.), R21 AG062985 (M.M), R37AG13925 (JLK, TT) PO1 AG043376 (PDR), U19 AG056278 (PDR), and PO1AG062413 (JLK, TT, PDR). JLK and TT are also supported by the Connor Fund, Robert J. and Theresa W. Ryan, and the Noaber Foundation. A portion of this work was supported by NASA-Florida Space Grant Consortium, 66016A30 grant “Biomanufacturing of Vascularized Tissues”, and by the NASA (SSERVI16) Cooperative Agreement (NNH16ZDA001N) program titled “Radiation Effects on Volatiles and Exploration of Asteroids and Lunar Surfaces (REVEALS)”, 80ARC017M0007.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to American Aging Association.

Keywords

  • Apoptosis
  • Cellular senescence
  • Pre-Adipocytes
  • Visceral adipose tissue
  • miR-146a-5p

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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