Research Paper Volume 16, Issue 3 pp 2005—2025
The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut
- 1 Institute of Nanobio Convergence, Pusan National University, Busan 46241, Republic of Korea
- 2 Department of Molecular Biology, Pusan National University, Busan 46241, Republic of Korea
- 3 Aging and Metabolism Research Group, Korea Food Research Institute, Wanju 55365, Republic of Korea
Received: February 14, 2023 Accepted: January 4, 2024 Published: February 7, 2024
https://doi.org/10.18632/aging.205518How to Cite
Copyright: © 2024 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Adult stem cells are pivotal for maintaining tissue homeostasis, and their functional decline is linked to aging and its associated diseases, influenced by the niche cells’ environment. Age- and cancer-related reduction of vitamin D and its receptor levels are well documented in human clinical studies. However, the mechanisms through which the vitamin D/vitamin D receptor pathway contributes to anti-aging and extends life expectancy are not well understood. In this study, we aimed to determine the protective role of the vitamin D/vitamin D receptor pathway in differentiated enterocytes (ECs) during intestinal stem cell (ISC) aging. By utilizing a well- established Drosophila midgut model for stem cell aging biology, we revealed that vitamin D receptor knockdown in ECs induced ISC proliferation, EC death, ISC aging, and enteroendocrine cell differentiation. Additionally, age- and oxidative stress-induced increases in ISC proliferation and centrosome amplification were reduced by vitamin D treatment. Our findings suggest a direct evidence of the anti-aging role of the vitamin D/vitamin D receptor pathway and provides insights into the molecular mechanisms underlying healthy aging in Drosophila.
Abbreviations
ISC: intestinal stem cell; EB: enteroblast; EC: enterocyte; EE: enteroendocrine; VDR: vitamin D receptor; GFP: green fluorescent protein; DAPI: 4’,6-diamidino-2-phenylindole; SD: standard deviation; γH2AvD: phosphorylated Drosophila histone variant of H2A (Ser137); EGFR: epidermal growth factor receptor; JNK: c-Jun N-terminal kinase; PH3: phosphorylated histone H3; HP1: heterochromatin protein 1; TOR: target of rapamycin; PVR: PDGF- and VEGF-receptor related; ATM/ATR: ataxia telangiectasia-mutated (ATM) and ATM- and RAD3-related (ATR).