- This research introduces a new approach to suppressing aging by stabilizing chromatin structure.

The research team, led by Professor Hyunsung Park from the Department of Life Sciences at the University of Seoul, reported an epigenetic mechanism in which a hypoxic microenvironment delays cellular aging.

These findings appeared in Nucleic Acids Research (2024 Impact Factor 13.1, top 4.06% in JCR field).

The first author of this paper is Dr. Soojeong Chang, who earned her Ph.D. from the Department of Life Sciences at the University of Seoul, and the corresponding author is Professor Hyunsung Park. 

It has been observed that cell division is suppressed and cellular aging is delayed in low-oxygen environments, which are often found within tumor tissues or bone marrow; however, the underlying molecular mechanism has remained unclear. 

In this study, the research team found that histone methylation increases in hypoxic environments. This increase inhibits histone cleavage by Cathepsin L, which prevents the collapse of higher-order chromatin structures and suppresses aging. 

In collaboration with Professor Sang-Won Lee's team at Korea University, the team conducted top-down proteomics analysis. This led to the first identification of new cleavage sites on H2B and H4 that were previously unknown in the Raf-induced aging process, which adds significant academic value.

Professor Park stated, "This study demonstrates that the hypoxic microenvironment suppresses cellular aging not merely by regulating specific gene expression, but by stabilizing the entire chromatin structure." She added, "By revealing the interactions among multi-layered epigenetic regulation involving histone methylation, histone cleavage, nuclear envelope, and chromatin binding, we have expanded the paradigm of aging research."

▶ Professor Hyunsung Park, Dr. Soojeong Chang

This research suggests potential applications in various research and clinical fields, including aging-control strategies that use hypoxic conditions, improving understanding of cancer and stem-cell microenvironments, and developing epigenetics-based therapeutic approaches for aging.

This study was conducted as part of the National Research Foundation of Korea's Basic Research Laboratory project, “Novel methods for deciphering of the cellular experiences embedded in the histone codes” (Principal Investigator: Professor Hyunsung Park).