NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. / Fang, Evandro F; Hou, Yujun; Lautrup, Sofie; Jensen, Martin Borch; Yang, Beimeng; SenGupta, Tanima; Caponio, Domenica; Khezri, Rojyar; Demarest, Tyler G; Aman, Yahyah; Figueroa, David; Morevati, Marya; Lee, Ho-Joon; Kato, Hisaya; Kassahun, Henok; Lee, Jong-Hyuk; Filippelli, Deborah; Okur, Mustafa Nazir; Mangerich, Aswin; Croteau, Deborah L; Maezawa, Yoshiro; Lyssiotis, Costas A; Tao, Jun; Yokote, Koutaro; Rusten, Tor Erik; Mattson, Mark P; Jasper, Heinrich; Nilsen, Hilde; Bohr, Vilhelm A.

In: Nature Communications, Vol. 10, No. 1, 5284, 2019.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Fang, EF, Hou, Y, Lautrup, S, Jensen, MB, Yang, B, SenGupta, T, Caponio, D, Khezri, R, Demarest, TG, Aman, Y, Figueroa, D, Morevati, M, Lee, H-J, Kato, H, Kassahun, H, Lee, J-H, Filippelli, D, Okur, MN, Mangerich, A, Croteau, DL, Maezawa, Y, Lyssiotis, CA, Tao, J, Yokote, K, Rusten, TE, Mattson, MP, Jasper, H, Nilsen, H & Bohr, VA 2019, 'NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome', Nature Communications, vol. 10, no. 1, 5284. https://doi.org/10.1038/s41467-019-13172-8

APA

Fang, E. F., Hou, Y., Lautrup, S., Jensen, M. B., Yang, B., SenGupta, T., Caponio, D., Khezri, R., Demarest, T. G., Aman, Y., Figueroa, D., Morevati, M., Lee, H-J., Kato, H., Kassahun, H., Lee, J-H., Filippelli, D., Okur, M. N., Mangerich, A., ... Bohr, V. A. (2019). NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications, 10(1), [5284]. https://doi.org/10.1038/s41467-019-13172-8

Vancouver

Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications. 2019;10(1). 5284. https://doi.org/10.1038/s41467-019-13172-8

Author

Fang, Evandro F ; Hou, Yujun ; Lautrup, Sofie ; Jensen, Martin Borch ; Yang, Beimeng ; SenGupta, Tanima ; Caponio, Domenica ; Khezri, Rojyar ; Demarest, Tyler G ; Aman, Yahyah ; Figueroa, David ; Morevati, Marya ; Lee, Ho-Joon ; Kato, Hisaya ; Kassahun, Henok ; Lee, Jong-Hyuk ; Filippelli, Deborah ; Okur, Mustafa Nazir ; Mangerich, Aswin ; Croteau, Deborah L ; Maezawa, Yoshiro ; Lyssiotis, Costas A ; Tao, Jun ; Yokote, Koutaro ; Rusten, Tor Erik ; Mattson, Mark P ; Jasper, Heinrich ; Nilsen, Hilde ; Bohr, Vilhelm A. / NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. In: Nature Communications. 2019 ; Vol. 10, No. 1.

Bibtex

@article{45ca976778aa45c39272ce322b6fbc57,
title = "NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome",
abstract = "Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD+, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD+ levels counteracts WS phenotypes.",
author = "Fang, {Evandro F} and Yujun Hou and Sofie Lautrup and Jensen, {Martin Borch} and Beimeng Yang and Tanima SenGupta and Domenica Caponio and Rojyar Khezri and Demarest, {Tyler G} and Yahyah Aman and David Figueroa and Marya Morevati and Ho-Joon Lee and Hisaya Kato and Henok Kassahun and Jong-Hyuk Lee and Deborah Filippelli and Okur, {Mustafa Nazir} and Aswin Mangerich and Croteau, {Deborah L} and Yoshiro Maezawa and Lyssiotis, {Costas A} and Jun Tao and Koutaro Yokote and Rusten, {Tor Erik} and Mattson, {Mark P} and Heinrich Jasper and Hilde Nilsen and Bohr, {Vilhelm A}",
year = "2019",
doi = "10.1038/s41467-019-13172-8",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome

AU - Fang, Evandro F

AU - Hou, Yujun

AU - Lautrup, Sofie

AU - Jensen, Martin Borch

AU - Yang, Beimeng

AU - SenGupta, Tanima

AU - Caponio, Domenica

AU - Khezri, Rojyar

AU - Demarest, Tyler G

AU - Aman, Yahyah

AU - Figueroa, David

AU - Morevati, Marya

AU - Lee, Ho-Joon

AU - Kato, Hisaya

AU - Kassahun, Henok

AU - Lee, Jong-Hyuk

AU - Filippelli, Deborah

AU - Okur, Mustafa Nazir

AU - Mangerich, Aswin

AU - Croteau, Deborah L

AU - Maezawa, Yoshiro

AU - Lyssiotis, Costas A

AU - Tao, Jun

AU - Yokote, Koutaro

AU - Rusten, Tor Erik

AU - Mattson, Mark P

AU - Jasper, Heinrich

AU - Nilsen, Hilde

AU - Bohr, Vilhelm A

PY - 2019

Y1 - 2019

N2 - Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD+, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD+ levels counteracts WS phenotypes.

AB - Metabolic dysfunction is a primary feature of Werner syndrome (WS), a human premature aging disease caused by mutations in the gene encoding the Werner (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but the underlying mechanisms are not understood, and whether the metabolic deficit can be targeted for therapeutic intervention has not been determined. Here we report impaired mitophagy and depletion of NAD+, a fundamental ubiquitous molecule, in WS patient samples and WS invertebrate models. WRN regulates transcription of a key NAD+ biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). NAD+ repletion restores NAD+ metabolic profiles and improves mitochondrial quality through DCT-1 and ULK-1-dependent mitophagy. At the organismal level, NAD+ repletion remarkably extends lifespan and delays accelerated aging, including stem cell dysfunction, in Caenorhabditis elegans and Drosophila melanogaster models of WS. Our findings suggest that accelerated aging in WS is mediated by impaired mitochondrial function and mitophagy, and that bolstering cellular NAD+ levels counteracts WS phenotypes.

U2 - 10.1038/s41467-019-13172-8

DO - 10.1038/s41467-019-13172-8

M3 - Journal article

C2 - 31754102

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5284

ER -

ID: 236986472