Publication

Targeting senescent cells alleviates obesity-induced metabolic dysfunction

Palmer, A. K., Xu, M., Zhu, Y., Pirtskhalava, T., Weivoda, M. M., Hachfeld, C. M., Prata, L. G., van Dijk, T. H., Verkade, E., Casaclang-Verzosa, G., Johnson, K. O., Cubro, H., Doornebal, E. J., Ogrodnik, M., Jurk, D., Jensen, M. D., Chini, E. N., Miller, J. D., Matveyenko, A., Stout, M. B., Schafer, M. J., White, T. A., Hickson, L. J., Demaria, M., Garovic, V., Grande, J., Arriaga, E. A., Kuipers, F., von Zglinicki, T., LeBrasseur, N. K., Campisi, J., Tchkonia, T. & Kirkland, J. L., Jun-2019, In : Aging Cell. 18, 3, 15 p., 12950.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Palmer, A. K., Xu, M., Zhu, Y., Pirtskhalava, T., Weivoda, M. M., Hachfeld, C. M., ... Kirkland, J. L. (2019). Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell, 18(3), [12950]. https://doi.org/10.1111/acel.12950

Author

Palmer, Allyson K. ; Xu, Ming ; Zhu, Yi ; Pirtskhalava, Tamar ; Weivoda, Megan M. ; Hachfeld, Christine M. ; Prata, Larissa G. ; van Dijk, Theo H. ; Verkade, Esther ; Casaclang-Verzosa, Grace ; Johnson, Kurt O. ; Cubro, Hajrunisa ; Doornebal, Ewald J. ; Ogrodnik, Mikolaj ; Jurk, Diana ; Jensen, Michael D. ; Chini, Eduardo N. ; Miller, Jordan D. ; Matveyenko, Aleksey ; Stout, Michael B. ; Schafer, Marissa J. ; White, Thomas A. ; Hickson, LaTonya J. ; Demaria, Marco ; Garovic, Vesna ; Grande, Joseph ; Arriaga, Edgar A. ; Kuipers, Folkert ; von Zglinicki, Thomas ; LeBrasseur, Nathan K. ; Campisi, Judith ; Tchkonia, Tamar ; Kirkland, James L. / Targeting senescent cells alleviates obesity-induced metabolic dysfunction. In: Aging Cell. 2019 ; Vol. 18, No. 3.

Harvard

Palmer, AK, Xu, M, Zhu, Y, Pirtskhalava, T, Weivoda, MM, Hachfeld, CM, Prata, LG, van Dijk, TH, Verkade, E, Casaclang-Verzosa, G, Johnson, KO, Cubro, H, Doornebal, EJ, Ogrodnik, M, Jurk, D, Jensen, MD, Chini, EN, Miller, JD, Matveyenko, A, Stout, MB, Schafer, MJ, White, TA, Hickson, LJ, Demaria, M, Garovic, V, Grande, J, Arriaga, EA, Kuipers, F, von Zglinicki, T, LeBrasseur, NK, Campisi, J, Tchkonia, T & Kirkland, JL 2019, 'Targeting senescent cells alleviates obesity-induced metabolic dysfunction' Aging Cell, vol. 18, no. 3, 12950. https://doi.org/10.1111/acel.12950

Standard

Targeting senescent cells alleviates obesity-induced metabolic dysfunction. / Palmer, Allyson K.; Xu, Ming; Zhu, Yi; Pirtskhalava, Tamar; Weivoda, Megan M.; Hachfeld, Christine M.; Prata, Larissa G.; van Dijk, Theo H.; Verkade, Esther; Casaclang-Verzosa, Grace; Johnson, Kurt O.; Cubro, Hajrunisa; Doornebal, Ewald J.; Ogrodnik, Mikolaj; Jurk, Diana; Jensen, Michael D.; Chini, Eduardo N.; Miller, Jordan D.; Matveyenko, Aleksey; Stout, Michael B.; Schafer, Marissa J.; White, Thomas A.; Hickson, LaTonya J.; Demaria, Marco; Garovic, Vesna; Grande, Joseph; Arriaga, Edgar A.; Kuipers, Folkert; von Zglinicki, Thomas; LeBrasseur, Nathan K.; Campisi, Judith; Tchkonia, Tamar; Kirkland, James L.

In: Aging Cell, Vol. 18, No. 3, 12950, 06.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Palmer AK, Xu M, Zhu Y, Pirtskhalava T, Weivoda MM, Hachfeld CM et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell. 2019 Jun;18(3). 12950. https://doi.org/10.1111/acel.12950


BibTeX

@article{681231e6174a4cdd9bf6fea1fbf3c53c,
title = "Targeting senescent cells alleviates obesity-induced metabolic dysfunction",
abstract = "Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible {"}suicide{"} genes driven by the p16(Ink4a) promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra-abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity-related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity-related metabolic dysfunction and its complications.",
keywords = "adipogenesis, aging, cellular senescence, dasatinib, quercetin, senolytics, type 2 diabetes, CELLULAR SENESCENCE, INSULIN-RESISTANCE, TISSUE, PHARMACOKINETICS, DIFFERENTIATION, PROLIFERATION, ADIPOGENESIS, MACROPHAGES, NAVITOCLAX, CLEARANCE",
author = "Palmer, {Allyson K.} and Ming Xu and Yi Zhu and Tamar Pirtskhalava and Weivoda, {Megan M.} and Hachfeld, {Christine M.} and Prata, {Larissa G.} and {van Dijk}, {Theo H.} and Esther Verkade and Grace Casaclang-Verzosa and Johnson, {Kurt O.} and Hajrunisa Cubro and Doornebal, {Ewald J.} and Mikolaj Ogrodnik and Diana Jurk and Jensen, {Michael D.} and Chini, {Eduardo N.} and Miller, {Jordan D.} and Aleksey Matveyenko and Stout, {Michael B.} and Schafer, {Marissa J.} and White, {Thomas A.} and Hickson, {LaTonya J.} and Marco Demaria and Vesna Garovic and Joseph Grande and Arriaga, {Edgar A.} and Folkert Kuipers and {von Zglinicki}, Thomas and LeBrasseur, {Nathan K.} and Judith Campisi and Tamar Tchkonia and Kirkland, {James L.}",
note = "{\circledC} 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.",
year = "2019",
month = "6",
doi = "10.1111/acel.12950",
language = "English",
volume = "18",
journal = "Aging Cell",
issn = "1474-9718",
publisher = "WILEY",
number = "3",

}

RIS

TY - JOUR

T1 - Targeting senescent cells alleviates obesity-induced metabolic dysfunction

AU - Palmer, Allyson K.

AU - Xu, Ming

AU - Zhu, Yi

AU - Pirtskhalava, Tamar

AU - Weivoda, Megan M.

AU - Hachfeld, Christine M.

AU - Prata, Larissa G.

AU - van Dijk, Theo H.

AU - Verkade, Esther

AU - Casaclang-Verzosa, Grace

AU - Johnson, Kurt O.

AU - Cubro, Hajrunisa

AU - Doornebal, Ewald J.

AU - Ogrodnik, Mikolaj

AU - Jurk, Diana

AU - Jensen, Michael D.

AU - Chini, Eduardo N.

AU - Miller, Jordan D.

AU - Matveyenko, Aleksey

AU - Stout, Michael B.

AU - Schafer, Marissa J.

AU - White, Thomas A.

AU - Hickson, LaTonya J.

AU - Demaria, Marco

AU - Garovic, Vesna

AU - Grande, Joseph

AU - Arriaga, Edgar A.

AU - Kuipers, Folkert

AU - von Zglinicki, Thomas

AU - LeBrasseur, Nathan K.

AU - Campisi, Judith

AU - Tchkonia, Tamar

AU - Kirkland, James L.

N1 - © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

PY - 2019/6

Y1 - 2019/6

N2 - Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible "suicide" genes driven by the p16(Ink4a) promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra-abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity-related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity-related metabolic dysfunction and its complications.

AB - Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible "suicide" genes driven by the p16(Ink4a) promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra-abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity-related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity-related metabolic dysfunction and its complications.

KW - adipogenesis

KW - aging

KW - cellular senescence

KW - dasatinib

KW - quercetin

KW - senolytics

KW - type 2 diabetes

KW - CELLULAR SENESCENCE

KW - INSULIN-RESISTANCE

KW - TISSUE

KW - PHARMACOKINETICS

KW - DIFFERENTIATION

KW - PROLIFERATION

KW - ADIPOGENESIS

KW - MACROPHAGES

KW - NAVITOCLAX

KW - CLEARANCE

U2 - 10.1111/acel.12950

DO - 10.1111/acel.12950

M3 - Article

VL - 18

JO - Aging Cell

JF - Aging Cell

SN - 1474-9718

IS - 3

M1 - 12950

ER -

ID: 78918102