Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver
It is known that the activities of nicotine adenine dinucleotide (NAD<sup>+</sup>)-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...
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MDPI AG
2022-05-01
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| Series: | Cells |
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| author | Chengting Luo Wenxi Ding Songbiao Zhu Yuling Chen Xiaohui Liu Haiteng Deng |
| author_facet | Chengting Luo Wenxi Ding Songbiao Zhu Yuling Chen Xiaohui Liu Haiteng Deng |
| author_sort | Chengting Luo |
| collection | DOAJ |
| description | It is known that the activities of nicotine adenine dinucleotide (NAD<sup>+</sup>)-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. |
| first_indexed | 2024-03-10T03:10:17Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:10:17Z |
| publishDate | 2022-05-01 |
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| series | Cells |
| spelling | doaj.art-10c9a8db9f394648892554083fbce3482023-11-23T10:27:45ZengMDPI AGCells2073-44092022-05-011110165410.3390/cells11101654Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse LiverChengting Luo0Wenxi Ding1Songbiao Zhu2Yuling Chen3Xiaohui Liu4Haiteng Deng5Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, ChinaTsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, ChinaTsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaMOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, ChinaIt is known that the activities of nicotine adenine dinucleotide (NAD<sup>+</sup>)-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.https://www.mdpi.com/2073-4409/11/10/1654acetylomeagingnicotinamide mononucleotideNAD (P) transhydrogenasefatty acid β oxidationTCA cycle |
| spellingShingle | Chengting Luo Wenxi Ding Songbiao Zhu Yuling Chen Xiaohui Liu Haiteng Deng Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver Cells acetylome aging nicotinamide mononucleotide NAD (P) transhydrogenase fatty acid β oxidation TCA cycle |
| title | Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver |
| title_full | Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver |
| title_fullStr | Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver |
| title_full_unstemmed | Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver |
| title_short | Nicotinamide Mononucleotide Administration Amends Protein Acetylome of Aged Mouse Liver |
| title_sort | nicotinamide mononucleotide administration amends protein acetylome of aged mouse liver |
| topic | acetylome aging nicotinamide mononucleotide NAD (P) transhydrogenase fatty acid β oxidation TCA cycle |
| url | https://www.mdpi.com/2073-4409/11/10/1654 |
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