(A) Survival curves of WT and Siglec-E−/− male (n = 59–62) and female (n = 58–59) littermates. Data are from two independent cohorts (cohort 1 included 31 WT and 38 Siglec-E−/− males, 31 WT and 33 Siglec-E−/− females. Cohort 2 included 28 WT and 23 Siglec-E−/− males, 27 WT and 26 Siglec-E−/− females). Log-rank test analysis showed significant differences in the survival curves both in males and females (males: χ2 = 5.833, d.f. = 1 and p = 0.0157; females: χ2 = 8.821, d.f. = 1 and p = 0.0030). (B and C) Mice at 80 weeks were assessed for spatial learning and memory via Barnes maze. Latency to escape (B) and number of errors before finding the escape box (C) are indicated in 3-day interval. Error bars reflect mean ± s.e.m. (n = 11). p was calculated with a Student's t test. (D) Hair graying of males was evaluated by three independent observers in a blind test. Average rank scores for each mouse are indicated. Error bars reflect mean ± s.e.m. (n = 9–11). p was calculated with a Student's t test. (E) Surviving mice were sacrificed at 100 weeks of age. Representative field of β-galactosidase staining of liver. Arrows indicate cells with increased localized staining. Scale bar is 100 μm. (F) Skin epidermal thickness was measured for WT and Siglec-E−/−. Mean and s.e.m. are indicated, n = 12, p was calculated with a Student's t test.