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bioRxiv · 10.1101/2022.02.24.481867

Conserved neuropeptidergic regulation of intestinal integrity in invertebrate models of aging

Singh, A.·Kaduskar, B.·Reddy, K. C.·Kumsta, C.·Bier, E.·Hansen, M.·Chalasani, S. H.
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Abstract

Age-related decline in intestinal barrier function impacts survival across species, but the underlying cell intrinsic and extrinsic factors remain unclear. Here, we demonstrate a role for neuropeptides in regulating aging-associated increases in intestinal leakiness. Adult-specific knockdown of insulin-like peptides daf-28 or ins-7 in C. elegans neurons or dilp3 in D. melanogaster neurons improves intestinal integrity and lifespan of these animals, respectively. Neuropeptide knockdowns activate intestinal DAF-16/FOXO transcription factor that likely increases expression of epithelial barrier components. Furthermore, age-associated changes in neuronal DAF-28 peptide secretion mirrors C. elegans reproductive span and overexpression of this peptide suppresses the improved intestinal health in long-lived germline-less animals. Collectively, we show that intestinal integrity is subject to neuronal regulation, and this neuropeptidergic axis may be modulated by the animals germline.

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Singh, A., Kaduskar, B., Reddy, K. C., Kumsta, C., Bier, E., Hansen, M., Chalasani, S. H.. 2022-02-28. Conserved neuropeptidergic regulation of intestinal integrity in invertebrate models of aging. https://doi.org/10.1101/2022.02.24.481867

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