A Virus-acquired Host Cytokine Controls Systemic Aging by Antagonizing Apoptosis

Aging is characterized by degeneration of unique tissues. However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine, Diedel, that when secreted from muscle or adipose can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and extend lifespan. Secreted homologs of Diedel are also found in viruses, having been acquired from host genomes. Focusing on potential mechanistic overlap between cellular aging and viral-host cell interactions and, we found that Diedel is a functionally conserved inhibitor of apoptosis and can act as a systemic rheostat to modulate cell death during aging. These results highlight a key role for secreted antagonists of apoptosis in the systemic coordination of tissue aging. Intact fly thorax and midguts were dissected (at 10 days and 30 days) in PBS. Total RNA was extracted using Trizol reagent and used as template to generate sample libraries for RNA sequencing (using the TruSeq Stranded Total RNA Library Prep Kit). Sample libraries were sequenced using the Illumina HiSeq 2500. Sequence cluster identification, quality pre-filtering, base calling and uncertainty assessment were done in real time using Illumina’s HCS 2.2.58 and RTA 1.18.64 software with default parameter settings. Between 7 and 12 million (1X50) base pair reads were generated per library and mapped to the Drosophila genome (Release 6).