title: Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia.
abstract: Aging of immune organs, termed as immunosenescence, is suspected to promote systemic inflammation and age-associated disease. The cause of immunosenescence and how it promotes disease, however, has remained unclear. We report that the Drosophila fat body, a major immune organ, undergoes immunosenescence and mounts strong systemic inflammation that leads to deregulation of immune deficiency (IMD) signaling in the midgut of old animals. Inflamed old fat bodies secrete circulating peptidoglycan recognition proteins that repress IMD activity in the midgut, thereby promoting gut hyperplasia. Further, fat body immunosenecence is caused by age-associated lamin-B reduction specifically in fat body cells, which then contributes to heterochromatin loss and derepression of genes involved in immune responses. As lamin-associated heterochromatin domains are enriched for genes involved in immune response in both Drosophila and mammalian cells, our findings may provide insights into the cause and consequence of immunosenescence during mammalian aging. PAPERFLICK:
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA. Electronic address: zheng@ciwemb.edu.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000375:Aging; D000818:Animals; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D005216:Fat Body / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D006570:Heterochromatin; D007249:Inflammation / Q000276:immunology; D034921:Lamin Type B / Q000378:metabolism*; D008322:Mammals / Q000276:immunology; D023421:Models, Animal; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D006570:Heterochromatin; D034921:Lamin Type B