https://phaidra.vetmeduni.ac.at/o:3002 Adult stem cell activity in naked mole rats for long-term tissue maintenance Montazid, Shamir Shamir Montazid 0000-0002-4584-5619 University of Oxford Irshad, Shazia Shazia Irshad 0000-0003-4536-373X University of Oxford Tomlinson, Ian Ian Tomlinson 0000-0003-3037-1470 University of Oxford Bennett, Nigel C. Nigel C. Bennett University of Pretoria East, James E. James E. East 0000-0001-8035-3700 John Radcliffe Hospital Bodmer, Walter F. Walter F. Bodmer University of Oxford Koth, Jana Jana Koth 0000-0002-6388-9308 University of Oxford Tessitore, Annamaria Annamaria Tessitore Novo Nordisk Research Centre Oxford Han, Jiangmeng Jiangmeng Han Rutgers University Liu, Yue Yue Liu Rutgers University Hayee, Bu'Hussain Bu'Hussain Hayee King's College Ziolkowski, Piotr Piotr Ziolkowski Wroclaw Medical University Gazinska, Patrycja Patrycja Gazinska Polish Center for Technology Development Rost, Fabian Fabian Rost 0000-0001-6466-2589 Technische Universität Dresden Altrock, Philipp M. Philipp M. Altrock 0000-0001-7731-3345 Max Planck Institute for Evolutionary Biology Bansal, Mukesh Mukesh Bansal Bristol Myers Squibb Wernisch, Bettina Bettina Wernisch University of Veterinary Medicine Vienna Penn, Dustin J. Dustin J. Penn 0000-0002-5406-8065 University of Veterinary Medicine Vienna Thrumurthy, Sri G. Sri G. Thrumurthy King's College Johnson, Brian Brian Johnson 0000-0002-9477-4677 University of California Gao, Nan Nan Gao Rutgers University Bandyopadhyay, Sheila Sheila Bandyopadhyay Rutgers University Hart, Daniel W. Daniel W. Hart University of Pretoria Nature Portfolio text eng The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity and tissue function with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in their native in vivo state, we find an expanded pool of Lgr5+ cells in NMRs, and these cells specifically at the crypt base (Lgr5+CBC) exhibit slower division rates compared to those in short-lived mice but have a similar turnover as human LGR5+CBC cells. Instead of entering quiescence (G0), NMR Lgr5+CBC cells reduce their division rates by prolonging arrest in the G1 and/or G2 phases of the cell cycle. Moreover, we also observe a higher proportion of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust pro-apoptotic, anti-proliferative response within the stem/progenitor cell zone. Mice; Humans; Animals; Longevity; Intestinal Mucosametabolism; Intestines; Adult Stem Cellsmetabolism; Receptors, G-Protein-Coupledmetabolism; Mole Rats http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:3002/download 10.1038/s41467-023-44138-6 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Nature Communications 14(1) (2023) Nature Communications 14 1 1.97 MB 2023