Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver

Cells. 2022 May 16;11(10):1654. doi: 10.3390/cells11101654.


It is known that the activities of nicotine adenine dinucleotide (NAD+)-dependent deacetylase decline in the aging mouse liver, and nicotinamide mononucleotide (NMN)-mediated activation of deacetylase has been shown to increase healthspans. However, age-induced changes of the acetylomic landscape and effects of NMN treatment on protein acetylation have not been reported. Here, we performed immunoprecipitation coupled with label-free quantitative LC-MS/MS (IPMS) to identify the acetylome and investigate the effects of aging and NMN on liver protein acetylation. In total, 7773 acetylated peptides assigned to 1997 proteins were commonly identified from young and aged livers treated with vehicle or NMN. The major biological processes associated with proteins exhibiting increased acetylation from aged livers were oxidation-reduction and metabolic processes. Proteins with decreased acetylation from aged livers mostly participated in transport and translation processes. Furthermore, NMN treatment inhibited the aging-related increase of acetylation on proteins regulating fatty acid β oxidation, the tricarboxylic acid (TCA) cycle and valine degradation. In particular, NAD (P) transhydrogenase (NNT) was markedly hyperacetylated at K70 in aged livers, and NMN treatment decreased acetylation intensity without altering protein levels. Acetylation at cytochrome 3a25 (Cyp3a25) at K141 was also greatly increased in aged livers, and NMN treatment totally arrested this increase. Our extensive identification and analysis provide novel insight and potential targets to combat aging and aging-related functional decline.

Keywords: NAD (P) transhydrogenase; TCA cycle; acetylome; aging; fatty acid β oxidation; nicotinamide mononucleotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Liquid
  • Liver / metabolism
  • Mice
  • NAD* / metabolism
  • Nicotinamide Mononucleotide* / pharmacology
  • Tandem Mass Spectrometry


  • NAD
  • Nicotinamide Mononucleotide

Grants and funding

This study was supported by National Natural Science Foundation of China (grant NO. 82172556) and Beijing Municipal Science and Technology Commission (NO. 5214025).