DNA Damage as a Signal for Systemic Aging: Beyond Repair Failure

Edisnap· Feb 24, 2026

This infographic illustrates the hypothesis that localized DNA damage triggers systemic aging by activating PARP, p53, and NF-κB, leading to widespread inflammation and tissue decline, contrasting this with a state where this signaling is mitigated.

What if DNA damage isn't just a consequence of aging but an active signaling mechanism that coordinates tissue-wide decline? The DDR doesn't just repair—it broadcasts.

This hypothesis explores how localized DNA damage triggers systemic responses through PARP activation, p53 signaling, and NF-κB-mediated inflammation, potentially explaining why aging is synchronized across tissues.