The divergent 3D genome landscapes of aging and neurodegenerative mouse models.

Aging and neurodegenerative mouse models show both shared and distinct early chromatin changes, with aged neurons maintaining TADs while pathological models show disorganization.

• Why it matters: Understanding how chromatin structure deteriorates during aging and neurodegeneration can reveal early markers and mechanisms underlying these conditions, addressing a key gap in neurobiology.
• What they did: The study used Hi-C to analyze cortical neurons from adult, aged, and SIRT6-knockout mice, comparing these data to Alzheimer’s disease model data stratified by γH2AX levels, focusing on chromatin interactions and organization.
• The result: Aged neurons retain TADs and short-range interactions, while neurodegenerative models show reduced TAD prominence and disorganized compartments, with changes correlating to increased DNA damage, suggesting aging primes chromatin for further breakdown.