PT - JOURNAL ARTICLE AU - Dehn, Ari S. AU - Gogna, Navdeep AU - Nishina, Patsy M. AU - Losick, Vicki P. TI - Blocking cell fusion inhibits age-induced polyploidy and maintains epithelial organization in <em>Drosophila</em> AID - 10.1101/2021.08.09.455651 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.08.09.455651 4099 - http://biorxiv.org/content/early/2021/08/09/2021.08.09.455651.short 4100 - http://biorxiv.org/content/early/2021/08/09/2021.08.09.455651.full AB - A characteristic of normal aging and age-related diseases is the remodeling of a tissue’s cellular organization through polyploid cell growth. Polyploidy arises from an increase in nuclear ploidy or the number of nuclei per cell. However, it is not known whether age-induced polyploidy is an adaption to stressors or a precursor to degeneration. Here, we find that the adult fruit fly’s abdominal epithelium becomes polyploid with age through generation of large multinucleated cells that make up more than 40% of the tissue area. The syncytia arise by cell fusion, not endomitosis. Epithelial multinucleation is also a characteristic of macular degeneration, including Ctnna1tvrm5, a mouse model for pattern dystrophy. Similarly, we find that the knockdown of alpha-catenin enhances multinucleation in the fly epithelium. We further show that age-induced polyploidy can be suppressed by inhibiting cell fusion revealing a means to maintain tissue organization in older animals.Competing Interest StatementThe authors have declared no competing interest.