Citations 2
Author response: Targeting senescent cells enhances adipogenesis and metabolic function in old age
Ding, Husheng, Weivoda, Megan , Pirtskhalava, Tamar , White, Thomas A. , Sepe, Anna, Johnson, Kurt O. , Giorgadze, Nino, Jensen, Michael D. , Kirkland, James L. , Xu, Ming , Palmer, Allyson K. , Stout, Michael B , LeBrasseur, Nathan K. , Tchkonia, Tamar
No container title available | February 4, 2016 | Volume: No volume available | Issue: No issue available | Pages: No page available
Targeting senescent cells enhances adipogenesis and metabolic function in old age
Xu, Ming , Palmer, Allyson K. , Ding, Husheng, Weivoda, Megan , Pirtskhalava, Tamar , White, Thomas A. , Sepe, Anna, Johnson, Kurt O. , Giorgadze, Nino, Jensen, Michael D. , LeBrasseur, Nathan K. , Tchkonia, Tamar , Kirkland, James L. , Weivoda, Megan M, Stout, Michael B, Stout, Michael B , Xu, Ming , Tchkonia, T , LeBrasseur, Nathan K , Palmer, Allyson K
eLife | December 19, 2015 | Volume: 4 | Issue: No issue available | Pages: No page available
Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18-month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22-month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism.