Figure 2. Genetic depletion of the p65 subunit of NF-κB delays aging symptoms and chronic diseases in progeroid Ercc1^–/Δ mice.

(A) EMSA on nuclear extracts from passage 5 WT, Ercc1^–/–, Ercc1^–/–p65^+/–, and Ercc1^–/–p65^–/– MEFs grown at 20% O₂ to measure NF-κB activity after depletion of p65. (B) Ercc1^–/Δ and Ercc1^–/Δp65^+/– mice were evaluated biweekly for the onset of spontaneous symptoms associated with aging. The aging score, which represents the fraction of aging symptoms delayed in a particular mouse compared with its sibling, for littermate pairs of Ercc1^–/Δ (red) and Ercc1^–/Δp65^+/– (orange) mice is a measure of healthspan (11). The mean aging score for each genotype is represented by a black bar. (C) Representative images of Ercc1^–/Δ and Ercc1^–/Δp65^+/– sex-matched littermates at 15 weeks of age. (D) Histopathologic changes in Ercc1^–/Δp65^+/– and Ercc1^–/Δ mice. Liver sections from 10-week-old mice were stained with oil red O to detect neutral lipids (hepatic steatosis; original magnification, ×100). Kidney specimens from 15-week-old mice were stained with H&E to detect proteinaceous renal tubular hyaline casts and glomerulosclerosis (original magnification, ×20). Cerebellar sections from 10-week-old mice were immunostained for GFAP (red), a marker of neurodegeneration. Nuclei were counterstained with DAPI (blue; original magnification, ×40). μCT of the vertebrae to assess bone porosity (for quantification, see Supplemental Figure 3A).