Fig. 1: Overview of heterochromatin loss during aging.

In young and healthy individuals, cells exhibit intact heterochromatin, a high level of H3K9me3, and a high level of HP1 bound to H3K9me3, which are factors that stabilize the heterochromatin complex. However, both chronologically and prematurely aged cells show decreased expression of core histones and reduced levels of H3K9me3 and HP1. CSB, WRN, and LMNA deficiency leads to H3, SETDB1, SUV39H1, and HP1 dysregulation, resulting in heterochromatin loss, DNA damage accumulation, and the expression of aberrant transcripts. The mechanisms under the decreased expression of CSB, WRN, and LMN with normal aging remain unclear.