Quantitative Acetylomics Reveals Dynamics of Protein Lysine Acetylation in Mouse Livers During Aging and Upon the Treatment of Nicotinamide Mononucleotide

Lysine acetylation is a reversible and dynamic post-translational modification that plays vital roles in regulating multiple cellular processes including aging. However, acetylome-wide analysis in the aging process remains poorly studied in mammalian tissues. Nicotinamide adenine dinucleotide (NAD+), a hub metabolite, benefits health span at least in part due to the activation of Sirtuins, a family of NAD+-consuming deacetylases, indicating changes in acetylome. Here, we combine two antibodies for the enrichment of acetylated peptides and perform label-free quantitative acetylomic analysis of mouse livers during natural aging and upon the treatment of beta-nicotinamide mononucleotide (NMN), a NAD+ booster. Our study describes previously unknown acetylation sites and reveals the acetylome-wide dynamics with age as well as upon the treatment of NMN. We discover protein acetylation events as potential aging biomarkers. We demonstrate that the life-beneficial effect of NMN could be partially reflected by the changes in age-related protein acetylation. Our quantitative assessment indicates that NMN has mild effects on acetylation sites previously reported as substrates of Sirtuins. Collectively, our data analyze protein acetylation with age, laying critical foundation for the functional study of protein post-translational modification essential for healthy aging and perhaps disease conditions. [Display omitted] •Acetylomes from mouse livers are studied with age and NMN treatment.•Protein acetylation events are discovered as potential aging biomarkers.•Life-beneficial effect of NMN could be partly reflected by acetylation changes.•NMN has mild effects on acetylation sites reported as substrates of Sirtuins. Li et al. have performed label-free quantification of the acetylomes in mouse livers with age and upon the treatment of nicotinamide mononucleotide (NMN), revealing previously unknown acetylation events. The datasets characterize not just the dynamics of acetylation with age but also specific acetylation sites as new aging biomarkers. The investigation indicates that the life-beneficial effect of NMN could be partially reflected by the changes in age-related protein acetylation. NMN has mild effects on acetylation previously reported as substrates of Sirtuins.