Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages

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Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. / Covarrubias, Anthony J.; Kale, Abhijit; Perrone, Rosalba; Lopez-Dominguez, Jose Alberto; Pisco, Angela Oliveira; Kasler, Herbert G.; Schmidt, Mark S.; Heckenbach, Indra; Kwok, Ryan; Wiley, Christopher D.; Wong, Hoi Shan; Gibbs, Eddy; Iyer, Shankar S.; Basisty, Nathan; Wu, Qiuxia; Kim, Ik Jung; Silva, Elena; Vitangcol, Kaitlyn; Shin, Kyong Oh; Lee, Yong Moon; Riley, Rebeccah; Ben-Sahra, Issam; Ott, Melanie; Schilling, Birgit; Scheibye-Knudsen, Morten; Ishihara, Katsuhiko; Quake, Stephen R.; Newman, John; Brenner, Charles; Campisi, Judith; Verdin, Eric.

I: Nature Metabolism, Bind 2, Nr. 11, 2020, s. 1265-1283.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Covarrubias, AJ, Kale, A, Perrone, R, Lopez-Dominguez, JA, Pisco, AO, Kasler, HG, Schmidt, MS, Heckenbach, I, Kwok, R, Wiley, CD, Wong, HS, Gibbs, E, Iyer, SS, Basisty, N, Wu, Q, Kim, IJ, Silva, E, Vitangcol, K, Shin, KO, Lee, YM, Riley, R, Ben-Sahra, I, Ott, M, Schilling, B, Scheibye-Knudsen, M, Ishihara, K, Quake, SR, Newman, J, Brenner, C, Campisi, J & Verdin, E 2020, 'Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages', Nature Metabolism, bind 2, nr. 11, s. 1265-1283. https://doi.org/10.1038/s42255-020-00305-3

APA

Covarrubias, A. J., Kale, A., Perrone, R., Lopez-Dominguez, J. A., Pisco, A. O., Kasler, H. G., Schmidt, M. S., Heckenbach, I., Kwok, R., Wiley, C. D., Wong, H. S., Gibbs, E., Iyer, S. S., Basisty, N., Wu, Q., Kim, I. J., Silva, E., Vitangcol, K., Shin, K. O., ... Verdin, E. (2020). Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nature Metabolism, 2(11), 1265-1283. https://doi.org/10.1038/s42255-020-00305-3

Vancouver

Covarrubias AJ, Kale A, Perrone R, Lopez-Dominguez JA, Pisco AO, Kasler HG o.a. Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nature Metabolism. 2020;2(11):1265-1283. https://doi.org/10.1038/s42255-020-00305-3

Author

Covarrubias, Anthony J. ; Kale, Abhijit ; Perrone, Rosalba ; Lopez-Dominguez, Jose Alberto ; Pisco, Angela Oliveira ; Kasler, Herbert G. ; Schmidt, Mark S. ; Heckenbach, Indra ; Kwok, Ryan ; Wiley, Christopher D. ; Wong, Hoi Shan ; Gibbs, Eddy ; Iyer, Shankar S. ; Basisty, Nathan ; Wu, Qiuxia ; Kim, Ik Jung ; Silva, Elena ; Vitangcol, Kaitlyn ; Shin, Kyong Oh ; Lee, Yong Moon ; Riley, Rebeccah ; Ben-Sahra, Issam ; Ott, Melanie ; Schilling, Birgit ; Scheibye-Knudsen, Morten ; Ishihara, Katsuhiko ; Quake, Stephen R. ; Newman, John ; Brenner, Charles ; Campisi, Judith ; Verdin, Eric. / Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. I: Nature Metabolism. 2020 ; Bind 2, Nr. 11. s. 1265-1283.

Bibtex

@article{5014f77bcbec48c4a4e5c6566715ac7d,
title = "Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages",
abstract = "Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.",
author = "Covarrubias, {Anthony J.} and Abhijit Kale and Rosalba Perrone and Lopez-Dominguez, {Jose Alberto} and Pisco, {Angela Oliveira} and Kasler, {Herbert G.} and Schmidt, {Mark S.} and Indra Heckenbach and Ryan Kwok and Wiley, {Christopher D.} and Wong, {Hoi Shan} and Eddy Gibbs and Iyer, {Shankar S.} and Nathan Basisty and Qiuxia Wu and Kim, {Ik Jung} and Elena Silva and Kaitlyn Vitangcol and Shin, {Kyong Oh} and Lee, {Yong Moon} and Rebeccah Riley and Issam Ben-Sahra and Melanie Ott and Birgit Schilling and Morten Scheibye-Knudsen and Katsuhiko Ishihara and Quake, {Stephen R.} and John Newman and Charles Brenner and Judith Campisi and Eric Verdin",
year = "2020",
doi = "10.1038/s42255-020-00305-3",
language = "English",
volume = "2",
pages = "1265--1283",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer",
number = "11",

}

RIS

TY - JOUR

T1 - Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages

AU - Covarrubias, Anthony J.

AU - Kale, Abhijit

AU - Perrone, Rosalba

AU - Lopez-Dominguez, Jose Alberto

AU - Pisco, Angela Oliveira

AU - Kasler, Herbert G.

AU - Schmidt, Mark S.

AU - Heckenbach, Indra

AU - Kwok, Ryan

AU - Wiley, Christopher D.

AU - Wong, Hoi Shan

AU - Gibbs, Eddy

AU - Iyer, Shankar S.

AU - Basisty, Nathan

AU - Wu, Qiuxia

AU - Kim, Ik Jung

AU - Silva, Elena

AU - Vitangcol, Kaitlyn

AU - Shin, Kyong Oh

AU - Lee, Yong Moon

AU - Riley, Rebeccah

AU - Ben-Sahra, Issam

AU - Ott, Melanie

AU - Schilling, Birgit

AU - Scheibye-Knudsen, Morten

AU - Ishihara, Katsuhiko

AU - Quake, Stephen R.

AU - Newman, John

AU - Brenner, Charles

AU - Campisi, Judith

AU - Verdin, Eric

PY - 2020

Y1 - 2020

N2 - Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.

AB - Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.

U2 - 10.1038/s42255-020-00305-3

DO - 10.1038/s42255-020-00305-3

M3 - Journal article

C2 - 33199924

AN - SCOPUS:85096043878

VL - 2

SP - 1265

EP - 1283

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

IS - 11

ER -

ID: 251939287