Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventions
BackgroundAs a critical molecule in biological systems, nicotinamide adenine dinucleotide (NAD+) influences the aging of mammals. Therefore, regulation of NAD+ synthesis and degradation may slow aging and mitigate related diseases.ResultsThis study investigated how mammalian tissues rely on differen...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Aging |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fragi.2025.1546017/full |
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| author | Fengjiao Huo Meili Zhao Yue Liu Shuyao Lv Shengyu Feng Liuling Guo Nan Wang Shuaishuai Zhang Qing Liu Taotao Mi Hao Wang Jian-Kang Zhu Hailiang Liu Hailiang Liu Hailiang Liu |
| author_facet | Fengjiao Huo Meili Zhao Yue Liu Shuyao Lv Shengyu Feng Liuling Guo Nan Wang Shuaishuai Zhang Qing Liu Taotao Mi Hao Wang Jian-Kang Zhu Hailiang Liu Hailiang Liu Hailiang Liu |
| author_sort | Fengjiao Huo |
| collection | DOAJ |
| description | BackgroundAs a critical molecule in biological systems, nicotinamide adenine dinucleotide (NAD+) influences the aging of mammals. Therefore, regulation of NAD+ synthesis and degradation may slow aging and mitigate related diseases.ResultsThis study investigated how mammalian tissues rely on different NAD+ synthesis pathways and prefer specific NAD+ precursors. Overexpressing the bacterial nicotinamidase PncA in mice increased NAD+ levels in the liver and kidneys but decreased levels in the heart and hippocampus. In aged mice (25 months old), this overexpression delayed aging indicators by boosting NAD+ levels in the liver and kidneys, indicating potential for PncA to improve age-related decline in these tissues. However, in younger mice (4 months old), PncA overexpression accelerates the senescence of cardiac cells, resulting in a reduction of NAD + levels, increased aging markers, and cognitive decline. These disparate results underscore the necessity of a nuanced, tissue-specific perspective when contemplating the use of NAD+ precursor supplementation as a means of addressing aging.ConclusionOur study highlights the complexity of NAD+ metabolism and its effects on aging in various tissues. It suggests personalized interventions for aging and age-related diseases by showing how different tissues respond to NAD+ precursor manipulation, emphasizing the importance of targeted strategies for optimal therapeutic results with minimal side effects. |
| format | Article |
| id | doaj-art-92e0c7e70cdd44afb412ff83b0386be4 |
| institution | OA Journals |
| issn | 2673-6217 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging |
| spelling | doaj-art-92e0c7e70cdd44afb412ff83b0386be42025-08-20T02:28:49ZengFrontiers Media S.A.Frontiers in Aging2673-62172025-04-01610.3389/fragi.2025.15460171546017Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventionsFengjiao Huo0Meili Zhao1Yue Liu2Shuyao Lv3Shengyu Feng4Liuling Guo5Nan Wang6Shuaishuai Zhang7Qing Liu8Taotao Mi9Hao Wang10Jian-Kang Zhu11Hailiang Liu12Hailiang Liu13Hailiang Liu14State Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaInstitute of Advanced Biotechnology and School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaState Key Laboratory of Cardiology and Medical Innovation Center, Institute for Regenerative Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaInstitute of Advanced Biotechnology and School of Medicine, Southern University of Science and Technology, Shenzhen, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi, ChinaBackgroundAs a critical molecule in biological systems, nicotinamide adenine dinucleotide (NAD+) influences the aging of mammals. Therefore, regulation of NAD+ synthesis and degradation may slow aging and mitigate related diseases.ResultsThis study investigated how mammalian tissues rely on different NAD+ synthesis pathways and prefer specific NAD+ precursors. Overexpressing the bacterial nicotinamidase PncA in mice increased NAD+ levels in the liver and kidneys but decreased levels in the heart and hippocampus. In aged mice (25 months old), this overexpression delayed aging indicators by boosting NAD+ levels in the liver and kidneys, indicating potential for PncA to improve age-related decline in these tissues. However, in younger mice (4 months old), PncA overexpression accelerates the senescence of cardiac cells, resulting in a reduction of NAD + levels, increased aging markers, and cognitive decline. These disparate results underscore the necessity of a nuanced, tissue-specific perspective when contemplating the use of NAD+ precursor supplementation as a means of addressing aging.ConclusionOur study highlights the complexity of NAD+ metabolism and its effects on aging in various tissues. It suggests personalized interventions for aging and age-related diseases by showing how different tissues respond to NAD+ precursor manipulation, emphasizing the importance of targeted strategies for optimal therapeutic results with minimal side effects.https://www.frontiersin.org/articles/10.3389/fragi.2025.1546017/fullagingnicotinamide adenine dinucleotidenicotinamidenicotinic acidpncA |
| spellingShingle | Fengjiao Huo Meili Zhao Yue Liu Shuyao Lv Shengyu Feng Liuling Guo Nan Wang Shuaishuai Zhang Qing Liu Taotao Mi Hao Wang Jian-Kang Zhu Hailiang Liu Hailiang Liu Hailiang Liu Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventions Frontiers in Aging aging nicotinamide adenine dinucleotide nicotinamide nicotinic acid pncA |
| title | Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventions |
| title_full | Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventions |
| title_fullStr | Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventions |
| title_full_unstemmed | Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventions |
| title_short | Tissue-specific effects of bacterial PncA overexpression on NAD+ metabolism and aging in mice: implications for tissue-specific aging interventions |
| title_sort | tissue specific effects of bacterial pnca overexpression on nad metabolism and aging in mice implications for tissue specific aging interventions |
| topic | aging nicotinamide adenine dinucleotide nicotinamide nicotinic acid pncA |
| url | https://www.frontiersin.org/articles/10.3389/fragi.2025.1546017/full |
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