The Aging Metabolome-Biomarkers to Hub Metabolites

Proteomics. 2020 Mar;20(5-6):e1800407. doi: 10.1002/pmic.201800407.


Aging biology is intimately associated with dysregulated metabolism, which is one of the hallmarks of aging. Aging-related pathways such as mTOR and AMPK, which are major targets of anti-aging interventions including rapamcyin, metformin, and exercise, either directly regulate or intersect with metabolic pathways. In this review, numerous candidate bio-markers of aging that have emerged using metabolomics are outlined. Metabolomics studies also reveal that not all metabolites are created equally. A set of core "hub" metabolites are emerging as central mediators of aging. The hub metabolites reviewed here are nicotinamide adenine dinucleotide, reduced nicotinamide dinucleotide phosphate, α-ketoglutarate, and β-hydroxybutyrate. These "hub" metabolites have signaling and epigenetic roles along with their canonical roles as co-factors or intermediates of carbon metabolism. Together these hub metabolites suggest a central role of the TCA cycle in signaling and metabolic dysregulation associated with aging.

Keywords: aging; hub metabolites; metabolomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • 3-Hydroxybutyric Acid / genetics
  • 3-Hydroxybutyric Acid / metabolism
  • Aging*
  • Animals
  • Biomarkers / metabolism
  • Citric Acid Cycle
  • DNA Damage
  • Epigenesis, Genetic
  • Humans
  • Ketoglutaric Acids / metabolism
  • Metabolic Networks and Pathways*
  • Metabolome*
  • Metabolomics / methods
  • NAD / genetics
  • NAD / metabolism
  • NADP / genetics
  • NADP / metabolism


  • Biomarkers
  • Ketoglutaric Acids
  • NAD
  • NADP
  • 3-Hydroxybutyric Acid