Protein and cell turnover parameters in healthy and progeroid tissues. (A and B) Protein turnover rates (k_t) (A) and predicted half-lives (t_1/2) (B) for proteins in tissues of healthy (gray) and progeroid (red) animals. These values are significantly different across tissues (P < 0.0001 for each genotype by Kruskal–Wallis test) and across genotypes (P < 0.0001 by Mann–Whitney test for each tissue). Box (Tukey) plot center line indicates median; box limits indicate 25th to 75th percentiles; whiskers indicate 1.5× interquartile range; points indicate outlier values. (C and D) Cell division rates (k_div) (C) and predicted cell doubling times (D) determined by TRAIL for tissues in healthy (gray) and progeroid (red) animals. Bars indicate standard error of the mean. * indicates that cell turnover rate is significantly faster in progeroid fat (P < 0.05, unpaired t test). (E) Only the proliferative intestine has a significant number of proteins whose k_t is equal to or lesser than k_div, suggesting that these proteins are diluted by cell division. (F) Cell cycle–corrected protein degradation rates (k_deg) determined for proteins in liver, fat, and heart muscle. *** indicates a significant decrease in protein turnover flux in progeroid tissues (P < 0.001, Mann–Whitney test). Data from wild-type animals reproduced from Hasper et al. (2023). (G) Comparison of protein abundance in progeroid tissues between proteins with significantly altered lifetime in progeroid tissue (blue) versus proteins with unchanged lifetime in progeroid tissue (gray). Tukey plot. **** indicates that proteins with impaired turnover in progeroid tissue are more abundant than proteins with unchanged turnover in progeroid tissue (****, P < 0.0001 by Mann–Whitney test).