(A) Representative photographs of 8-week-old LmnaG609G/G609G mice (female, left; male, right) treated with JH4 (10 mg/kg twice per week). Mice were injected 8 times (from 4 weeks of age). (B) Increase in BW of LmnaG609G/G609G mice following JH4 injection. P values were determined by Student’s t test. (C) Increase in muscle strength following JH4 injection. Grip strength was measured for LmnaG609G/G609G, Lmna+/G609G, Lmna+/+ male mice by pulling the spring balance after treatment with JH4 or vehicle alone. P value was determined by Student’s t test. (D) Growth morphology of thymus and spleen from 9-week-old LmnaG609G/G609G mice treated with vehicle or JH4. An obvious enlargement of both organs after JH4 treatment was observed. (E) JH4 injection time–dependent organ size increase. Compared with vehicle-injected mice, the size of several organs was gradually increased by treatment time. Numbers above each bar indicate the fold increase at each time point (see also Supplemental Figure 14). (F) JH4 injection promoted the cell cycle of splenocytes obtained from 7-week-old mice (injected 6 times). Cell-cycle promotion was observed in JH4-treated cells. (G) Rescue of cell and tissue defects. Foot pad skin was thickened and dermal connective tissue was enriched in JH4-treated animals (upper panels). Kidney tissue was well organized after JH4 treatment. Tissues were obtained from 18-week-old (vehicle) and 22-week-old (JH4) mice. Scale bar: 80 μm, original magnification ×100. (H) Increase in cell density and reduction of deformed cell nuclei in JH4-treated heart tissue obtained from the same mice above. On the basis of the histology, nuclear morphology (right) and cell density (left) were counted for 3 different mice and 5 different regions per mouse by 3 researchers. P values were determined by Student’s t test. (I) Representative images of heart muscle. Arrows indicate deformed nuclei. Scale bar: 10 μm. (J) JH4 suppressed progerin and induced RAD51 and phosphorylated CDC2 (p-CDC2). Western blot analysis was performed using extracts from liver and kidney tissue obtained from 18-week-old sibling mice.