Effect of methione restriction in the liver of WT and Lmna G609G KI mice

Dietary intervention constitutes a feasible approach for modulating metabolism and improving healthspan and lifespan. Methionine restriction (MR) delays the appearance of age-related diseases and increases longevity in normal mice. However, the effect of MR on premature aging remains to be elucidated. Here, we describe that MR extends lifespan in two different mouse models of Hutchinson-Gilford progeria syndrome (HGPS) by reversing the transcriptome alterations in inflammation and DNA-damage response genes present in this condition. Further, MR improves the lipid profile and alters the levels of bile acids, both in wild-type and in progeroid mice. Notably, treatment with the bile acid cholic acid improves healthspan and lifespan in vivo. These results suggest the existence of a metabolic pathway involved in the longevity extension achieved by MR and support the possibility of dietary interventions for treating progeria.

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Bárcena C, Quirós PM, Durand S, Mayoral P, Rodríguez F, Caravia XM, Mariño G, Garabaya C, Fernández-García MT, Kroemer G, Freije JMP, López-Otín C