Tier 3 — preclinical

SIRT6/RXRα/retinoic acid-related signaling contributes to intestinal stem cell homeostasis during aging and is modulated by Atractylenolide II

Yaqian Cao, Chunhui Song, Xiaoqing Sun, Zhenyu Niu, Xueni Zhang, Kerong Qi, Jiazhong Cai, Wenfeng Guo, Gang Chen, Ning Li, Yanwu Li
Chemico-Biological Interactions 2026 439:112316

Bibliography

PubMed
PMID 42660438
DOI
10.1016/j.cbi.2026.112316

Study snapshot

DesignAged-mouse, tissue-specific knockout and intestinal-organoid mechanistic study.
ModelYoung and aged mice, intestinal epithelial-specific Sirt6-deficient mice and 3D intestinal organoids.
SampleAnimal and organoid experimental cohorts.
InterventionSirt6 deletion/inhibition, RXRα and retinoic-acid pathway manipulation, and Atractylenolide II.
DurationAging and ex-vivo organoid experiments.
EndpointsVillus-to-crypt ratio; Intestinal stem-cell proliferation; SOX9; Lgr5; RXRα acetylation; Retinoic-acid metabolism

What the study showed, in plain terms

Aged intestine showed lower SIRT6 and impaired stem-cell homeostasis. Intestinal epithelial Sirt6 loss reproduced aging-like crypt and stem-cell defects, while Atractylenolide II partially improved SIRT6/RXRα/retinoic-acid pathway changes.

Key findings

SIRT6 physically associated with RXRα, and SIRT6 loss/inhibition altered RXRα acetylation and retinoic-acid balance alongside intestinal stem-cell dysfunction.

What this study can and cannot tell us

Preclinical mouse and organoid evidence; Atractylenolide II is not a validated human SIRT6 therapy; no clinical intestinal-aging outcomes.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability