GSE62580
Age-associated loss of lamin-B leads to systemic inflammation and gut hyperplasia
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 unexplored. We report that the  Drosophila fat body, a major immune organ, undergoes immunosenescence and mounts  strong systemic inflammation that leads to de-regulation 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 ageassociated  lamin-B reduction specifically in fat body cells, which then contributes to  heterochromatin loss and de-repression 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 aging. Overall design: 17 samples from the fat body, the midgut, or the whole gut with different ages or RNAi treatment. 6 of the samples were wildtype young control. For each experiment, we had two or three biological replicates.