Life expectancy in most developed countries has been rising over the past century. In the UK alone, there are about 12 million people over 65 years old and centenarians have increased by 85% in the past 15 years. As a result of the ageing population, which is due mainly to improvements in medical treatments, public health, improved housing and lifestyle choices, there is an associated increase in the prevalence of pathological conditions, such as metabolic disorders, type 2 diabetes, cardiovascular and neurodegenerative diseases, many types of cancer and others. Statistics suggest that nearly 54% of elderly people in the UK live with at least two chronic conditions, revealing the urgency for identifying interventions that can prevent and/or treat such disorders. Non-pharmacological, dietary interventions such as energetic restriction (ER) and methionine restriction (MR) have revealed promising outcomes in increasing longevity and preventing and/or reversing the development of ageing-associated disorders. In this review, we discuss the evidence and mechanisms that are involved in these processes. Fibroblast growth factor 1 and hydrogen sulphide are important molecules involved in the effects of ER and MR in the extension of life span. Their role is also associated with the prevention of metabolic and cognitive disorders, highlighting these interventions as promising modulators for improvement of health span.

Mammalian studies report that methionine restriction (MR) as a dietary regimen extends life span, delays the onset of age-related diseases and enhances fat oxidation in obese subjects with metabolic syndromes. However, the underlying cellular signalling pathways are poorly understood. Rainbow trout (Oncorhynchus mykiss) is a glucose-intolerant species, providing an excellent model for the study of carbohydrate metabolism. MR diets in combination with 12 % (+/ − ) and 22 % (+/ − ) carbohydrate-rich meals were fed to rainbow trout for a period of 8 weeks and phenotypic and transcript expression changes in the liver and white muscle were assessed. Fish fed MR diets, irrespective of carbohydrate load, were shown to abolish the glucose-intolerant phenotype 6 h post-feeding. There was a distinct switch in glucose and glycogen content in the liver of fish fed MR diets, with a significantly higher concentration of glycogen, suggesting reduced glycolytic capacity. Transcriptional responses to MR demonstrated decreased expression of hepatic fatty acid synthase, sterol regulatory binding protein 1, PPARγ coactivator 1-α and PPARα, indicative of a reduction in the de novo synthesis of fatty acids and cholesterol, and a potential decrease in hepatic fat oxidative capacity. Muscle adenylate charge was depressed under MR, and increased expression of AMP-activated protein kinase α1 was detected, indicative of reduced energy availability. Total DNA methylation showed that carbohydrate load, rather than MR, dictated hypomethylation of genomic DNA. This is the first study which demonstrates that MR can abolish a glucose-intolerant phenotype in trout, and identifies trout as a suitable model for studying metabolic syndromes.