Human fibroblasts from aged individuals exhibit chromosomal instability through replication stress caused by oxidative stress.

ABSTRACT: Aneuploid cells are known to increase with age. Previously, we demonstrated an increased number of aneuploid fibroblasts isolated from aged mice due to chromosomal instability (CIN), which is caused by oxidative stress. It is unclear whether this phenomenon also occurs in human cells, which are more resistant to oxidative stress than mouse cells. Here, we found that fibroblasts from aged individuals exhibited an increase in aneuploid cells. The frequency of chromosome missegregation and micronuclei increased in these cells, indicating CIN. A DNA fiber assay revealed the presence of replication stress, accompanied by an increase in 53BP1 nuclear bodies and ultrafine bridges. Increased levels of reactive oxygen species derived from mitochondria, along with reduced mitochondrial membrane pote

SUBMITTER: Zhu K 

PROVIDER: S-EPMC12749110 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature