Extended Data Fig. 7: LCA exerts rejuvenating activity in an TGR5-independent manner.

a-e, LCA can effectively enhance muscle functions in aged TGR5^−/− mice. The aged, ad libitum-fed TGR5^−/− mice were fed with (2-hydroxypropyl)-β-cyclodextrin-coated LCA at 1 g/l in drinking water for 1 month. The muscular NAD⁺ levels (a), mitochondrial areas (b), and mtDNA:nDNA ratios (c), grip strength (d), and running capacity (e), were then determined. Data are shown as mean ± s.e.m.; n = 6 (a, c), 106 (b), 35 (d, control), 40 (d, LCA), 11 (e) biological replicates for each genotype/treatment, and P value by two-sided Student’s t-test. f-j, iso-LCA does not enhance muscle functions in aged mice. Ad libitum-fed mice were fed with (2-hydroxypropyl)-β-cyclodextrin-coated iso-LCA at 1 g/l in drinking water for 1 month (f-i), followed by intramuscular injection of cardiotoxin to induce muscle damage (j). The muscular NAD⁺ levels (f), muscular mtDNA:nDNA ratios (g), muscle grip strength (h) and running distance (i), and muscle regeneration (j) were then determined. Results are mean ± s.e.m.; n = 6 (f, g), 30 (h) or 10 (i) biological replicates for each condition, and P value by two-sided Student’s t-test. Experiments in this figure were performed three times.

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