Dietary Restriction and Nutrient Balance in Aging

Abstract

Dietary regimens that favour reduced calorie intake delay aging and age-associated diseases. New evidences revealed that nutritional balance of dietary components without food restriction increases lifespan. Particular nutrients as several nitrogen sources, proteins, amino acid, and ammonium are implicated in life and healthspan regulation in different model organisms from yeast to mammals. Aging and dietary restriction interact through partially overlapping mechanisms in the activation of the conserved nutrient-signalling pathways, mainly the insulin/insulin-like growth factor (IIS) and the Target Of Rapamycin (TOR). The specific nutrients of dietary regimens, their balance, and how they interact with different genes and pathways are currently being uncovered. Taking into account that dietary regimes can largely influence overall human health and changes in risk factors such as cholesterol level and blood pressure, these new findings are of great importance to fully comprehend the interplay between diet and humans health.

Figure 1

Scheme of longevity regulatory pathways in various model organisms (yeast, worms, flies, and mammals). Identical symbols are used for the orthologous genes in each model organism. In worms, flies, and mammals, dietary restriction reduces signalling through IIS/TOR pathways, deactivating the PI3K/Akt/TOR intracellular signalling cascade and consequently activating the antiaging FOXO family transcription factor(s), known to regulate stress resistance and aging. In yeast, dietary restriction reduces the activity of the TOR/Sch9 and RAS/PKA nutrient-signalling pathways, both converging on the protein kinase Rim15 that in consequence activates its downstream transcription factors Gis1 and Msn2/4, involved in the postdiauxic shift (PDS) element-driven gene expression and stress-responsive elements (STRE) gene expression, respectively. The involvement of RAS signalling in longevity regulation is indicated in the two models where it has been described. lysine (Lys.), methionine (Met.), threonine (Thr.), and valine (Val.). The detailed description and other abbreviations are given in the text.

Figure 2

Schematic of nutrients (glucose, amino acids, and ammonium) that accelerate aging through different signalling pathways. A dietary balance between these nutrients is necessary for achieving maximum longevity in yeast. The detailed description and abbreviations are given in the text.