Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging
A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exer...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier BV
2020
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| Online Access: | https://hdl.handle.net/1721.1/126072 |
| _version_ | 1811092739766353920 |
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| author | Das, Abhirup Huang, George X. Bonkowski, Michael S. Longchamp, Alban Li, Catherine Schultz, Michael B. Kim, Lynn-Jee Osborne, Brenna Joshi, Sanket Lu, Yuancheng Treviño-Villarreal, Jose Humberto Kang, Myung-Jin Hung, Tzong-tyng Lee, Brendan Williams, Eric O Igarashi, Masaki Mitchell, James R. Wu, Lindsay E. Turner, Nigel Arany, Zolt Guarente, Leonard Pershing Sinclair, David A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Das, Abhirup Huang, George X. Bonkowski, Michael S. Longchamp, Alban Li, Catherine Schultz, Michael B. Kim, Lynn-Jee Osborne, Brenna Joshi, Sanket Lu, Yuancheng Treviño-Villarreal, Jose Humberto Kang, Myung-Jin Hung, Tzong-tyng Lee, Brendan Williams, Eric O Igarashi, Masaki Mitchell, James R. Wu, Lindsay E. Turner, Nigel Arany, Zolt Guarente, Leonard Pershing Sinclair, David A. |
| author_sort | Das, Abhirup |
| collection | MIT |
| description | A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly. Endothelial SIRT1 regulates pro-angiogenic signals secreted from myocytes and improves muscle health. Treatment of mice with NAD precursor nicotinamide mononucleotide improves vascular and increases endurance in aging mice. |
| first_indexed | 2024-09-23T15:24:21Z |
| format | Article |
| id | mit-1721.1/126072 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:24:21Z |
| publishDate | 2020 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1260722022-10-02T02:35:55Z Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging Das, Abhirup Huang, George X. Bonkowski, Michael S. Longchamp, Alban Li, Catherine Schultz, Michael B. Kim, Lynn-Jee Osborne, Brenna Joshi, Sanket Lu, Yuancheng Treviño-Villarreal, Jose Humberto Kang, Myung-Jin Hung, Tzong-tyng Lee, Brendan Williams, Eric O Igarashi, Masaki Mitchell, James R. Wu, Lindsay E. Turner, Nigel Arany, Zolt Guarente, Leonard Pershing Sinclair, David A. Massachusetts Institute of Technology. Department of Biology Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology) A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly. Endothelial SIRT1 regulates pro-angiogenic signals secreted from myocytes and improves muscle health. Treatment of mice with NAD precursor nicotinamide mononucleotide improves vascular and increases endurance in aging mice. Glenn Foundation for Medical Research (Award RO1 AG028730) Glenn Foundation for Medical Research (Award RO1 DK100263) NIH/NIA (Grant RO1 AG015339) 2020-07-07T18:26:50Z 2020-07-07T18:26:50Z 2018-03 2017-12 2019-12-05T16:10:13Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 https://hdl.handle.net/1721.1/126072 Das, Abhirup et al. "Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging." Cell 173, 1 (March 2018): 74-89 © 2018 Elsevier en http://dx.doi.org/10.1016/j.cell.2018.02.008 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Das, Abhirup Huang, George X. Bonkowski, Michael S. Longchamp, Alban Li, Catherine Schultz, Michael B. Kim, Lynn-Jee Osborne, Brenna Joshi, Sanket Lu, Yuancheng Treviño-Villarreal, Jose Humberto Kang, Myung-Jin Hung, Tzong-tyng Lee, Brendan Williams, Eric O Igarashi, Masaki Mitchell, James R. Wu, Lindsay E. Turner, Nigel Arany, Zolt Guarente, Leonard Pershing Sinclair, David A. Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging |
| title | Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging |
| title_full | Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging |
| title_fullStr | Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging |
| title_full_unstemmed | Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging |
| title_short | Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging |
| title_sort | impairment of an endothelial nad h2s signaling network is a reversible cause of vascular aging |
| url | https://hdl.handle.net/1721.1/126072 |
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