Untangling Determinants of Enhanced Health and Lifespan through a Multi-omics Approach in Mice

Cell Metab. 2020 Jul 7;32(1):100-116.e4. doi: 10.1016/j.cmet.2020.04.018. Epub 2020 May 14.

Abstract

The impact of chronic caloric restriction (CR) on health and survival is complex with poorly understood underlying molecular mechanisms. A recent study in mice addressing the diets used in nonhuman primate CR studies found that while diet composition did not impact longevity, fasting time and total calorie intake were determinant for increased survival. Here, integrated analysis of physiological and multi-omics data from ad libitum, meal-fed, or CR animals was used to gain insight into pathways associated with improved health and survival. We identified a potential involvement of the glycine-serine-threonine metabolic axis in longevity and related molecular mechanisms. Direct comparison of the different feeding strategies unveiled a pattern of shared pathways of improved health that included short-chain fatty acids and essential PUFA metabolism. These findings were recapitulated in the serum metabolome from nonhuman primates. We propose that the pathways identified might be targeted for their potential role in healthy aging.

Keywords: aging; calorie restriction; calories; dietary interventions; dietary restriction; fasting; meal fed; metabolism; metabolomics; time-restricted feeding.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Caloric Restriction*
  • Fatty Acids, Unsaturated / metabolism*
  • Female
  • Glucose / analysis
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Glycine / metabolism*
  • Longevity*
  • Male
  • Metabolomics
  • Mice
  • Mice, Inbred C57BL
  • Serine / metabolism*
  • Threonine / metabolism*

Substances

  • Fatty Acids, Unsaturated
  • Threonine
  • Serine
  • Glucose
  • Glycine