(A) Plasma LEAP2 decreased in Leap2 shRNA–injected mice. (B and C) Plasma ghrelin or total ghrelin levels showed no change in Leap2 shRNA–treated mice. (D) Plasma LEAP2/ghrelin ratio in old mice with or without LEAP2 modulation. (A–D) Vehicle shRNA, n = 21; Leap2 shRNA, n = 14. (E) Mouse freezing percentage in old mice with or without LEAP2 modulation. Vehicle shRNA, n = 9; Leap2 shRNA, n = 7. (F and G) Mouse novel object recognition in old mice with or without LEAP2 modulation. (F) Training phase with 2 identical objects. (G) Testing phase with 1 familiar object and 1 novel object. Vehicle shRNA, n = 13; Leap2 shRNA, n = 8. (H–J) Spatial navigation of old mice with or without LEAP2 modulation. (H) Spatial learning ability represented by the latency to find the hidden platform during the learning phase. (I) Spatial reference memory represented by platform cross number in the probing phase. (J) Swimming speed during probing phase. Vehicle shRNA, n = 8; Leap2 shRNA, n = 4. Unpaired Student’s t test. *P < 0.05, **P < 0.01, ***P < 0.001.