衰老科学杂志

抽象的

Centrosome Dysfunction and Senescence: Coincidence or Causality?

Delowar Hossain  and William Y. Tsang

Centrosomes are the tiny organelles found in most eukaryotic systems. By virtue of their ability to anchor, organize and nucleate microtubules, they play a crucial role in establishing spindle bipolarity and in ensuring the fidelity of cell division. Defects in centrosome structure and function often result in mitotic catastrophe, cell cycle arrest, cell death, genomic instability and/or aneuploidy, leading to human disorders such as primary microcephaly, cancer and ciliopathies. Interestingly, genomic instability and aneuploidy are also hallmarks of aging and cellular senescence, but our understanding of the connection between centrosome dysfunction and senescence remains rudimentary. In this review, we focus on existing evidence suggesting that these two phenomena are indeed related, along with the emerging view that centrosome aberrations represent a form of cellular stress that is necessary and sufficient to trigger a permanent cell cycle arrest and senescence. The molecular mechanisms underlying cellular senescence as a consequence of centrosome aberrations and the involvement of p53 will be discussed.