Cell
Volume 159, Issue 4, 6 November 2014, Pages 829-843
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Article
Age-Associated Loss of Lamin-B Leads to Systemic Inflammation and Gut Hyperplasia

https://doi.org/10.1016/j.cell.2014.10.028Get rights and content
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Highlights

  • Old flies exhibit fat body inflammation and midgut immune repression

  • Age-associated lamin-B loss in fat bodies causes uncontrolled systemic inflammation

  • Lamin-B loss in the old fat body triggers midgut immune repression and hyperplasia

  • PGRPs secreted by the old fat body inhibit midgut immunity and trigger hyperplasia

Summary

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.

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