Humanin is positively correlated with lifespan and is regulated by the GH/IGF-I axis in mice. (A–D) Plasma humanin levels were measured in (A) GH transgenic mice (GH-Tg) (N = 11/group), (B) Ames dwarf mice (N = 10/group), (C) liver igf1 gene deletion (LID) (N = 7/group), and (D) IGFBP-3 knockout (BP3KO) mice (N = 3/group); and respective matched controls.(E) Comparison of GH, IGF-I, HN levels and lifespan of each mouse model shown in panels A-D. (F) Male 12-week-old C57BL/6 mice (N = 8/group) were injected with human GH (2 mg kg−1 day−1, IP) or IGF-I (500 μg kg−1 day−1, BID, IP) for 20 days, and plasma was collected to measure humanin. Data are shown as mean ± SEM. Student’s t-test, *P < 0.05, **P < 0.01.