Genomic instability is a central hallmark of aging and is strongly associated with functional decline across cells, tissues, and organisms. Age-associated accumulation of DNA lesions has been documented in diverse model systems, including double-strand breaks, replication stress, chromosomal rearrangements, and epigenetic alterations. However, how distinct forms of genome instability relate to one another, and which types of damage most directly contribute to aging phenotypes, remains an open question.

Recent advances in imaging, quantitative analysis, and single-cell methodologies enable the direct visualization and measurement of genome instability across spatial and temporal scales. Approaches to detect DNA double-strand breaks, assess pathway-specific repair engagement, quantify mutation burden, map structural genome alterations, and monitor chromatin reorganization provide complementary yet often disconnected views of aging-associated damage. Integrating these methodologies is essential to move beyond correlation and toward a mechanistic dissection of how specific lesions, repair pathway dynamics, and genome architectural changes drive cellular aging.

This JoVE Collection will highlight experimental strategies that enable precise, quantitative, and spatially resolved analysis of genomic instability in aging cells and tissues. By bringing together imaging-based assays, repair pathway reporters, sequencing-based detection methods, and chromatin-level analyses, this collection aims to provide a cohesive framework for interrogating how genome instability contributes to aging and age-associated diseases. Together, these approaches will support a more integrated and mechanistic understanding of genome maintenance during aging.`