β-catenin-promoted cholesterol metabolism protects against cellular senescence in naked mole-rat cells

Woei Yaw Chee, Yuriko Kurahashi, Junhyeong Kim, Kyoko Miura, Daisuke Okuzaki, Tohru Ishitani, Kentaro Kajiwara, Shigeyuki Nada, Hideyuki Okano, Masato Okada

研究成果: Article査読

3 被引用数 (Scopus)

抄録

The naked mole-rat (NMR; Heterocephalus glaber) exhibits cancer resistance and an exceptionally long lifespan of approximately 30 years, but the mechanism(s) underlying increased longevity in NMRs remains unclear. In the present study, we report unique mechanisms underlying cholesterol metabolism in NMR cells, which may be responsible for their anti-senescent properties. NMR fibroblasts expressed β-catenin abundantly; this high expression was linked to increased accumulation of cholesterol-enriched lipid droplets. Ablation of β-catenin or inhibition of cholesterol synthesis abolished lipid droplet formation and induced senescence-like phenotypes accompanied by increased oxidative stress. β-catenin ablation downregulated apolipoprotein F and the LXR/RXR pathway, which are involved in cholesterol transport and biogenesis. Apolipoprotein F ablation also suppressed lipid droplet accumulation and promoted cellular senescence, indicating that apolipoprotein F mediates β-catenin signaling in NMR cells. Thus, we suggest that β-catenin in NMRs functions to offset senescence by regulating cholesterol metabolism, which may contribute to increased longevity in NMRs.

本文言語English
論文番号357
ジャーナルCommunications biology
4
1
DOI
出版ステータスPublished - 2021 12月

ASJC Scopus subject areas

  • 医学(その他)
  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)

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