Role of histone variants in aging and cancer

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

Aging affects all living organisms, causing cellular and organ-level changes, but the nuclear mechanisms behind it are not well understood, yet 90% of cancers are related to the aging process and significantly burden the elderly. This project focuses on chromatin changes during aging, specifically at the centromere, which is crucial for cell division and marked by the histone variant CENP-A. The study found that aging reduces CENP-A levels and alters chromatin structure, leading to centromere inactivation and mitotic defects in aged human cells, including healthy individuals. Reduced centromere transcription was also observed, and we successfully identified an epigenetic pathway regulating this process. By targeting epigenetic regulators, they successfully reactivated centromeres in aged cells. We are now studying how increased micronuclei formation in aging contributes to cancer initiation, potentially linking aging-related epigenetic changes (beyond DNA methylation) to cancer development when tumor suppressors like p53 are lost with a goal to take this work into 3D printed colon tumors, and using existing patient biobanked tumor and aging tissues.