SIRT1 alleviates high-magnitude compression-induced senescence in nucleus pulposus cells via PINK1-dependent mitophagy.

Aging
Yiyang WangPei Li

Abstract

Mechanical overloading-induced nucleus pulposus (NP) cells senescence plays an important role in the pathogenesis of intervertebral disc degeneration (IVDD). The silent mating type information regulator 2 homolog-1 (SIRT1)-mediated pathway preserves the normal NP cell phenotype and mitochondrial homeostasis under multiple stresses. We aimed to investigate the role of SIRT1 in IVDD by assessing the effects of SIRT1 overexpression on high-magnitude compression-induced senescence in NP cells. High-magnitude compression induced cellular senescence and mitochondrial dysfunction in human NP cells. Moreover, SIRT1 overexpression tended to alleviate NP cell senescence and mitochondrial dysfunction under compressive stress. Given the mitophagy-inducing property of SIRT1, activity of mitophagy was evaluated in NP cells to further demonstrate the underlying mechanism. The results showed that SIRT1-overexpression attenuated senescence and mitochondrial injury in NP cells subjected to high-magnitude compression. However, depletion of PINK1, a key mitophagic regulator, impaired mitophagy and blocked the protective role of SIRT1 against compression induced senescence in NP cells. In summary, these results suggest that SIRT1 plays a protective...Continue Reading

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Citations

Mar 26, 2021·Frontiers in Cell and Developmental Biology·Hao ZhuQiang Shen
May 15, 2021·Frontiers in Cell and Developmental Biology·Lu ZhaoZhengwei Yuan
Jul 18, 2021·Experimental & Molecular Medicine·Yu SongCao Yang
Oct 5, 2021·Experimental and Therapeutic Medicine·Zhidi LinJianyuan Jiang

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Methods Mentioned

BETA
transmission electron microscopy
flow cytometry
fluorescence
confocal
transfection
fluorescence microscopy
optical microscopy
confocal microscopy
electrophoresis

Software Mentioned

SPSS
AMT Advantage
Image Lab

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