Figure 1. Aging and Loss of SIRT1 Leads to a Specific Decline in Mitochondrial-Encoded Genes and Impairment in Mitochondrial Homeostasis in Skeletal Muscle.

(A) ATP content of 6-, 22-, and 30-month-old mice (n = 5, *p < 0.05 versus 6-month-old mice).

(B) Cytochrome c oxidase (COX) activity (n = 5, *p < 0.05 versus 6-month-old animals).

(C and D) Mitochondrial DNA content (C) and DNA integrity (D) (n = 5, *p < 0.05 versus 6-month-old animals).

(E) Expression of nuclear- and mitochondrially encoded genes (n = 5, *p < 0.05 versus 6-month-old animals).

(F) Immunoblot for COX2 and COX4 in 6-, 22-, and 30-month-old mice.

(G) Expression of nuclear- (NDUFS8, NDUFAS, SDHb, SDHd, Uqcrc1, Uqcrc2, COX5b, Cox6a1, ATP5a1, and ATPc1) and mitochondrially encoded genes (ND1, ND2, ND3, ND4, ND4l, ND5, ND6, Cytb, COX1, COX2, COX3, ATP6, and ATP8) in WT and SIRT1 iKO mice (n = 5, *p < 0.05 versus WT).

(H and I) (H) Immunoblot for COX2 and COX4 and (I) ATP content in WT and SIRT1 iKO mice (n = 5, *p < 0.05 versus WT).

(J) Mitochondrial DNA content of WT and SIRT1 iKO mice (n = 5, *p < 0.05 versus WT).

(K) Electron microscopy of gastrocnemius from WT and SIRT1 iKO mice and mitochondrial area (n = 4).

(L) Expression of nuclear- and mitochondrially encoded genes in SIRT1 flox/flox Cre-ERT2 primary myoblasts treated with vehicle (0 hr) or tamoxifen (OHT) to induce SIRT1 excision for 6, 12, 24, and 48 hr (n = 4, *p < 0.05 versus vehicle).

(M) Mitochondrial mass by NAO fluorescence in SIRT1 flox/flox Cre-ERT2 primary myoblasts treated with vehicle (0 hr) or OHT to induce SIRT1 excision for 6, 12, 24, and 48 hr (n = 4, *p < 0.05 versus vehicle).

Nuclear- and mitochondrially encoded genes were ND1, Cytb, COX1, ATP6 and NDUFS8, SDHb, Uqcrc1, COX5b, ATP5a1, respectively. Tissue samples are gastrocnemius unless otherwise stated. Values are expressed as mean ± SEM. See also Figure S1.