Fig. 1. The IL-11–ERK–mTORC1 signalling module is upregulated in ageing and associated with senescence and metabolic decline.
a, Signalling pathway by which IL-11 induces canonical STAT3 activation and non-canonical ERK activation, LKB1–AMPK inactivation and mTOR activation. b, Western blots of the indicated liver phosphoproteins from male mice aged 12–110 weeks (n = 5 per group); total (phosphorylated plus unphosphorylated) proteins are shown in Extended Data Fig. 1a. c, Heat map showing densitometry of IL-11 protein expression normalized to GAPDH (immunoblots are shown in Extended Data Fig. 1c) in gastrocnemius (gastroc) and vWAT from 12- to 110-week-old male mice (n = 5 per group). d, Representative immunofluorescence images (scale bars, 100 µm) of liver EGFP and SLC10A1 expression from 10 and 110-week-old Il11-EGFP mice and age-matched wild-type (WT) controls (n = 3 per group). Scale bars, 100 μm. e, Western blot of liver extracts from 10- and 110-week-old male wild-type and Il11ra1−/− mice (n = 5 per group); total proteins are shown in Extended Data Fig. 2a. f,g, Body weight (f) and percentages of fat and lean mass (male wild-type, n = 12; male Il11ra1−/−, n = 16; female wild-type, n = 15; female Il11ra1−/−, n = 13). h,i, Telomere length (h) and mtDNA copy number (i) in liver from young (10-week-old) and old (110-week-old) male and female wild-type and Il11ra1−/− mice (young male wild-type, n = 8; young male Il11ra1−/−, n = 7; old male wild-type, n = 11; old male Il11ra1−/−, n = 17; young female wild-type, n = 7; young female Il11ra1−/−, n = 8; old female wild-type, n = 15; old female Il11ra1−/−, n = 13). FC, fold change. j, IL-11 and GAPDH immunoblots from the indicated organs of 12- and 105-week-old male wild-type and Il11−/− mice (liver and soleus, n = 4 per group; vWAT and gastrocnemius, n = 6 per group). f–i, Data are mean ± s.d.; the table below each panel shows summary statistics from two-way ANOVA with Sidak’s correction. For gel source data, see Supplementary Fig. 1.