Figure 7.
Acute Simultaneous Deletion of OPA1 and FGF21 Reverted Precocious Epithelial Senescence, Systemic Inflammation, and Premature Death
(A) FGF21 plasma levels in OPA1/FGF21-KO, determined by ELISA, are significantly decreased compared to OPA1-deficient animals. Data are mean ± SEM, n = 4, ∗∗p < 0.01.
(B) Body weight measured 120 days after the beginning of tamoxifen treatment. Data are mean ± SEM, n = 5, ∗∗p < 0.01.
(C) Muscle weight of controls, Opa1−/−, and Opa1−/−Fgf21−/−. Data are mean ± SEM, n = 4, ∗∗p < 0.01. TA, tibialis anterior; GNM, gastrocnemius.
(D) Epididymal fat is higher in Opa1−/−Fgf21−/− than in Opa1−/− mice. Data are mean ± SEM (controls n = 4, Opa1−/− n = 8, Opa1−/−Fgf21−/− n = 4), ∗∗p < 0.01.
(E) Eight-month-old Opa1−/−Fgf21−/− show reduction of animal size (left panel) but do not show white hairs and kyphosis (right panel).
(F) Left panel: representative images of oil red O staining in liver cryosections. Right panel: Quantification of liver triglyceride content. Data are mean ± SEM, n = 4, ∗∗p < 0.01.
(G) Fasting blood glucose is restored to normal level in Opa1−/−Fgf21−/− mice. Data are mean ± SEM (Opa1f/f n = 4, Opa1−/− n = 8, Opa1−/−Fgf21−/− n = 4), ∗∗p < 0.01.
(H) Blood inflammatory cytokines are back to control level in Opa1−/−Fgf21−/− mice. Data are mean ± SEM, n = 4, ∗∗p < 0.01.
(I) Quantification of fibers number per muscle (left panel) and denervated NCAM-positive fibers (right panel) in Opa1−/−, Opa1−/−Fgf21−/−, and controls. Data are mean ± SEM, n = 5, ∗∗p < 0.01.
(J and K) Quantification of β-galactosidase and p21 levels. Data represent mean ± SEM, n = 4, ∗∗p < 0.01.
(L) Survival curve of control, Opa1−/−, and Opa1−/−Fgf21−/−mice. Data are mean ± SEM (controls n = 19, Opa1−/− n = 20, Opa1−/−Fgf21−/− n = 15), ∗∗p < 0.01.
(M) Regression analysis between age and FGF21 plasma levels of human subjects ranging from 19 to 103 years old. Data represent mean ± SEM, n = 180.