Werner Syndrome: Senescence-Associated Inflammation & Adipogenesis | Aging-US



October 25, 2023

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  • Aging-US published this trending research paper on October 3, 2023, in Volume 15, Issue 19, entitled, “Senescence-associated inflammation and inhibition of adipogenesis in subcutaneous fat in Werner syndrome" by researchers from the Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan; Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Chiba, Japan; Laboratory of Medical Omics Research, Kazusa DNA Research Institute, Kisarazu, Japan; Department of Omics Medicine, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Plastic, Reconstructive, And Aesthetic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan; Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan; Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan; Department of Pediatrics, International University of Welfare and Health School of Medicine, Narita, Japan. DOI - https://doi.org/10.18632/aging.205078 Corresponding authors - Hisaya Kato - hisayakato@chiba-u.jp, Yoshiro Maezawa - yoshiromaezawa@chiba-u.jp, and Koutaro Yokote - kyokote@faculty.chiba-u.jp Abstract Werner syndrome (WS) is a hereditary premature aging disorder characterized by visceral fat accumulation and subcutaneous lipoatrophy, resulting in severe insulin resistance. However, its underlying mechanism remains unclear. In this study, we show that senescence-associated inflammation and suppressed adipogenesis play a role in subcutaneous adipose tissue reduction and dysfunction in WS. Clinical data from four Japanese patients with WS revealed significant associations between the decrease of areas of subcutaneous fat and increased insulin resistance measured by the glucose clamp. Adipose-derived stem cells from the stromal vascular fraction derived from WS subcutaneous adipose tissues (WSVF) showed early replicative senescence and a significant increase in the expression of senescence-associated secretory phenotype (SASP) markers. Additionally, adipogenesis and insulin signaling were suppressed in WSVF, and the expression of adipogenesis suppressor genes and SASP-related genes was increased. Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), alleviated premature cellular senescence, rescued the decrease in insulin signaling, and extended the lifespan of WS model of C. elegans. To the best of our knowledge, this study is the first to reveal the critical role of cellular senescence in subcutaneous lipoatrophy and severe insulin resistance in WS, highlighting the therapeutic potential of rapamycin for this disease. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205078 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Werner syndrome, premature aging, lipodystrophy, stromal vascular fraction, SASP About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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