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Fig. S1 Representative telomerase telomere repeat amplification protocol assay in mouse embryonic fibroblasts treated with the indicated dose of TA-65 for 24 h and 5 days. A cellular extract from HCT116 cells was included as a positive control, and RNase was added in all experimental settings as negative control. IC, PCR efficiency control.

Fig. S2 Body weight of the indicated mice before or after treatment is given as mean ± SEM.

Fig. S3 (A) Fold change in mouse telomerase reverse transcriptase (mTERT) mRNA levels at 3 months post-treatment in different tissues of 1-year-old TA-65-treated mice compared to age-matched controls. Mouse telomerase reverse transcriptase mRNA values were normalized to actin. (B) Fold change in JunB mRNA levels at 3 months post-treatment in different tissues of 1-year-old TA-65-treated mice compared to age-matched nontreated controls. JunB mRNA values were normalized to actin. (C) Fold change in c-Myc mRNA levels at 3 months post-treatment in different tissues of 1-year-old TA-65-treated mice compared to age-matched nontreated controls. c-Myc mRNA values were normalized to actin.

Fig. S4 Fold changes in CD44, CyclinD1, Klf4, Fibronectin and p16 mRNA levels in liver extracts from TA-65-treated mice compared to age-matched nontreated controls. mRNA values were normalized to actin.

Fig. S5 (A) Percentage of Ki67-positive cells in the lungs of TA-65-treated or untreated (control) mice. Student’s t-test was used for statistical assessments. At least four high-power fields (HPF) (×100) were used per independent mouse and around 24 000 lung cells were scored per mouse. (B) Representative Ki67 immunohistochemistry images of lungs from TA-65-treated or untreated (control) mice. (C) Percentage of TUNEL-positive (Apoptag detection kit) cells in the lungs of TA-65-treated or untreated (control) mice. Student’s t-test was used for statistical assessments. At least four HPF (×100) were used per independent mouse and around 24 000 cells were scored per mouse. (D) Representative TUNEL stained images of lungs from TA-65-treated or untreated (control) mice. (E) Percentage of Ki67-positive cells in the liver of TA-65-treated or untreated (control) mice. Student’s t-test was used for statistical assessments. At least five HPF (×100) were used per independent mouse and around 3000 hepatocytes were scored per mouse. (F) Representative Ki67 immunohistochemistry images of the liver from TA-65-treated or untreated (control) mice. (G) Percentage of TUNEL-positive (Apoptag detection kit) cells in the liver of TA-65-treated or untreated (control) mice. Student’s t-test was used for statistical assessments. At least five HPF (×100) were used per independent mouse, and around 3000 hepatocytes were scored per mouse. (H) Representative TUNEL stained images of the liver from TA-65-treated or untreated (control) mice.

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