RRC ID 85383
著者 Qin P, Wang Q, Wu Y, You Q, Li M, Guo Z.
タイトル Age mosaic of gut epithelial cells prevents aging.
ジャーナル Nat Commun
Abstract Improving gut health by altering the activity of intestinal stem cells is thought to have the potential to reverse aging. The aged Drosophila midgut undergoes hyperplasia and barrier dysfunction. However, it is still unclear how to limit hyperplasia to extend lifespan. Here, we show that early midgut injury prevents the abrupt onset of aging hyperplasia and extends lifespan in flies. Daily transcriptome profiling and lineage tracing analysis show that the abrupt onset of aging hyperplasia is due to the collective turnover of developmentally generated "old" enterocytes (ECs). Early injury introduces new ECs into the old EC population, forming the epithelial age mosaic. Age mosaic avoids collective EC turnover and facilitates septate junction formation, thereby improving the epithelial barrier and extending lifespan. Furthermore, we found that intermittent time-restricted feeding benefits health by creating an EC age mosaic. Our findings suggest that age mosaic may become a therapeutic approach to reverse aging.
巻・号 16(1)
ページ 6734
公開日 2025-7-22
DOI 10.1038/s41467-025-62043-y
PII 10.1038/s41467-025-62043-y
PMID 40695820
PMC PMC12284232
MeSH Aging* / genetics Aging* / physiology Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / physiology Enterocytes / cytology Enterocytes / metabolism Epithelial Cells* / cytology Epithelial Cells* / metabolism Gene Expression Profiling Hyperplasia Intestinal Mucosa* / cytology Intestinal Mucosa* / metabolism Intestines / cytology Longevity / physiology Stem Cells / metabolism
IF 12.121
リソース情報
ショウジョウバエ 12074R-1 11415R-2