IBA researchers clarify pathways of lifespan extension by methionine restriction

Both the lifespan and healthspan of many species can be significantly extended by dietary restriction, i.e. applying specific diets with reduced content of carbohydrates, fat and/or protein. Lifespan extension by reduced dietary protein intake (protein restriction) is increasingly recognized as a convenient anti-ageing intervention. Even reducing just the concentration of a single amino acid, such as methionine, in the diet (methionine restriction, MetR) can extend the lifespan of many species including rodents. Effects of MetR on human lifespan and healthspan are not known.

IBA researchers, in collaboration with the group of Frank Madeo of Graz University, have now used the cellular senescence model to assess anti-ageing effects of MetR on human cells, using human diploid fibroblasts (HDF). It was found that MetR significantly extended replicative lifespan of such cells, thereby postponing cellular senescence. MetR significantly decreased activity of mitochondrial complex IV and diminished the accumulation of reactive oxygen species. Lifespan extension was accompanied by a significant decrease in the levels of subunits of mitochondrial complex IV, but also complex I, which was due to a decreased translation rate of several mtDNA-encoded subunits. Together, these findings indicate that MetR slows down aging in human cells by modulating mitochondrial protein synthesis and respiratory chain assembly (Aging Cell. 2014 Oct 1. doi: 10.1111/acel.12266. [Epub ahead of print]). We also found that lifespan extension by MetR in human cells is independent of increased autophagy. This is in contrast with previous findings in yeast, where methionine restriction (MetR) extended yeast chronological lifespan in an autophagy-dependent manner. (PLoS Genet. 2014 May 1;10(5):e1004347. doi: 10.1371). These studies shed new light on molecular mechanisms of lifespan extension by dietary restriction, and will in the future enable new targeted approaches for improving human healthspan.