Early onset of aging-like changes is restricted to cognitive abilities and skin structure in Cnr1^−/− mice

Partner recognition ability in Cnr1^+/+ and Cnr1^−/− mice. Reduction in time spent with social interactions in 2 consecutive trials is indicated as a function of age. The intertrial time was (A) 2 hours, (B) 4 hours, and (C) 8 hours. The sign of recognition is a significant difference in social time between the 2 presentations. Mean and standard error of the mean (SEM) of the percentage reduction in social time is shown. (D) Duration of partner recognition is reduced in 3-month-old Cnr1^−/− animals, whereas only 6-month-old wild-type animals showed first deficits in partner recognition. * p < 0.05; ** p < 0.01; *** p < 0.001; difference in social time between the first and second presentation (Student paired t-test).

Age-dependent changes in locomotor activity were measured as distance traveled in the open field. Although strains reached their maximum locomotor activity at different ages, the age-dependent decline in activity was similar between the genotypes. Mean values are shown, error bars represent standard error of the mean (SEM). * p < 0.05: ** p < 0.01; *** p < 0.001; significantly reduced activity compared with the age group with the highest locomotor activity (3-month-old in Cnr1^+/+ and 4-month-old in Cnr1^−/− mice) according to 1-way analysis of variance (ANOVA) followed by Bonferroni t-test. + p < 0.05; difference between wild-type and null-mutant animals according to 2-way ANOVA followed by Bonferroni t-test.

The age-dependent loss of hearing ability measured as the acoustic startle response intensity that was elicited by a 100 dB sound was similar between the genotypes in a wide frequency range. Mean ± standard error of the mean (SEM) is shown. * p < 0.05; ** p < 0.01; *** p < 0.001 significantly reduced activity than 2-month-old animals from the same genotype according to 1-way analysis of variance (ANOVA) followed by Bonferroni t-test.

(A) Atrophy of the testis assessed as percentage of cell-free areas within the seminiferous tubules was present in Cnr1^−/− mice in each age group. Significant age-dependent changes were detected only in wild-type mice. Columns represent group means, the error bars represent standard error of the mean (SEM). * p < 0.05 significant elevation in cell-free areas compared with 2-month-old animals; +++ p < 0.001 difference between wild-type and null-mutant animals; both according to 2-way analysis of variance (ANOVA) followed by Bonferroni t-test. (B) Representative histological structure of the testis of 2-, 5-, and 12-month old Cnr1^+/+ and Cnr1^−/− animals.

(A) The width of the subdermal fat layer was significantly reduced in 12-month-old Cnr1^−/− mice. Mean ± standard error of the mean (SEM) is shown. *** p < 0.001 difference between wild-type and null-mutant animals; according to 2-way analysis of variance (ANOVA) followed by Bonferroni t-test. (B) Representative histological structure of the skin of 2-, 5-, and 12-month old Cnr1^+/+ and Cnr1^−/− animals. a, epidermis; b, dermis; c, subdermal fat layer; d, muscle.