Citations 2
Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice
Tchkonia, Tamar , Pirtskhalava, Tamar , Berryman, Darlene E. , Lubbers, Ellen R. , Escande, Carlos , Spong, Adam, Oberg, Ann L. , Miller, Richard A. , Kopchick, John J. , Kirkland, James L. , Stout, Michael B, Tchkonia, Tamara, Palmer, Allyson K. , Stout, Michael B , List, Edward Owen , Masternak, Michal M , LeBrasseur, Nathan K. , Bartke, Andrzej , Tchkonia, T
Aging | March 6, 2016 | Volume: 6 | Issue: 7 | Pages: 575-586
JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age
Xu, Ming , Tchkonia, Tamar , Ding, Husheng, Ogrodnik, Mikołaj , Lubbers, Ellen R. , Pirtskhalava, Tamar , White, Thomas A. , Johnson, Kurt O. , Mezera, Vojtěch , Giorgadze, Nino, Jensen, Michael D. , LeBrasseur, Nathan K. , Kirkland, James L. , Tchkonia, Tamara, Stout, Michael B, Stout, Michael B , Xu, Ming , Tchkonia, T , LeBrasseur, Nathan K
Proceedings of the National Academy of Sciences | November 2, 2015 | Volume: 112 | Issue: 46 | Pages: No page available
Significance A hallmark of aging is chronic sterile inflammation, which is closely associated with frailty and age-related diseases. We found that senescent fat progenitor cells accumulate in adipose tissue with aging and acquire a senescence-associated secretory phenotype (SASP), with increased production of proinflammatory cytokines compared with nonsenescent cells. These cells provoked inflammation in adipose tissue and induced macrophage migration. The JAK pathway is activated in adipose tissue with aging, and the SASP can be suppressed by inhibiting the JAK pathway in senescent cells. JAK1/2 inhibitors reduced inflammation and alleviated frailty in aged mice. One possible mechanism contributing to reduced frailty is SASP inhibition. Our study points to the JAK pathway as a potential target for countering age-related dysfunction.