Long-term Dietary Macronutrients and Hepatic Gene Expression in Aging Mice

J Gerontol A Biol Sci Med Sci. 2018 Nov 10;73(12):1618-1625. doi: 10.1093/gerona/gly065.

Abstract

Nutrition influences both hepatic function and aging, but mechanisms are poorly understood. Here, the effects of lifelong, ad libitum-fed diets varying in macronutrients and energy on hepatic gene expression were studied. Gene expression was measured using Affymetrix mouse arrays in livers of 46 mice aged 15 months fed one of 25 diets varying in protein, carbohydrates, fat, and energy density from 3 weeks of age. Gene expression was almost entirely influenced by protein intake. Carbohydrate and fat intake had few effects on gene expression compared with protein. Pathways and processes associated with protein intake included those involved with mitochondrial function, metabolic signaling (PI3K-Akt, AMPK, mTOR) and metabolism of protein and amino acids. Protein intake had variable effects on genes associated with regulation of longevity and influenced by caloric restriction. Among the genes of interest with expression that were significantly associated with protein intake are Cth, Gls2, Igf1, and Nnmt, which were increased with higher protein intake, and Igf2bp2, Fgf21, Prkab2, and Mtor, which were increased with lower protein intake. Dietary protein has a powerful impact on hepatic gene expression in older mice, with some overlap with genes previously reported to be involved with regulation of longevity or caloric restriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Aging / genetics*
  • Aging / physiology
  • Animals
  • Diet / classification*
  • Dietary Carbohydrates / metabolism
  • Dietary Fats / metabolism
  • Dietary Proteins / metabolism
  • Disease Models, Animal
  • Energy Intake
  • Female
  • Fibroblast Growth Factors / genetics
  • Gene Expression Regulation*
  • Insulin-Like Growth Factor I / genetics
  • Liver / metabolism*
  • Liver Diseases / genetics
  • Longevity / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Micronutrients / administration & dosage*
  • Protein Kinases / genetics
  • Random Allocation
  • Sensitivity and Specificity
  • TOR Serine-Threonine Kinases / genetics

Substances

  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins
  • Fgf20 protein, mouse
  • Micronutrients
  • insulin-like growth factor-1, mouse
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor I
  • Protein Kinases
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinase Kinases