Tree Shrew as an Emerging Model for Aging Research: Characterization of Senescence and Therapeutic Interventions
7 affiliations
- 1State Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Healthy Aging Research of Yunnan Province Kunming Institute of Zoology, Chinese Academy of Sciences Kunming Yunnan China
- 2University of Chinese Academy of Sciences Beijing China
- 3National Resource Center for Non‐Human Primates, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) Kunming Institute of Zoology, Chinese Academy of Sciences Kunming Yunnan China
- 4School of Chemical Science and Technology Yunnan University Kunming Yunnan China
- 5Laboratory of Molecular Genetics of Aging and Tumor, Medical School Kunming University of Science and Technology Kunming Yunnan China
- 6Key Laboratory of Biodiversity Information Kunming Institute of Zoology, Chinese Academy of Sciences Kunming Yunnan China
- 7KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Yunnan China
Abstract
Aging is characterized by progressive physiological decline and increased susceptibility to age‐related diseases. Conventional rodent models have contributed significantly to our understanding of aging, yet their translational relevance is limited by substantial evolutionary divergence from humans. Here, we introduce the tree shrew ( Tupaia belangeri chinensis ) as a novel and biologically relevant model organism for aging research. In vitro, we induced cellular senescence in tree shrew fibroblasts through ionizing radiation, doxorubicin treatment, or replicative exhaustion, all of which consistently triggered robust senescent phenotypes and a pronounced senescence‐associated secretory phenotype (SASP), accompanied by upregulation of conserved senescence biomarkers. In vivo, aged tree shrews exhibited progressive physical frailty, metabolic dysfunction, organ fibroplasia, and spontaneous tumorigenesis. Transcriptomic profiling uncovered widespread age‐related alterations across multiple tissues, prominently affecting pathways involved in chronic inflammation, extracellular matrix remodeling, and metabolic dysregulation. Further comparative transcriptomic analyses of liver and spleen tissues confirmed that tree shrews recapitulate conserved human aging transcriptional trajectories and core gene expression patterns, whereas mice displayed markedly divergent aging signatures. Notably, senolytic intervention with dasatinib and quercetin (D + Q) effectively reversed key transcriptional changes and ameliorated selected age‐related pathologies, including hepatic steatosis. Importantly, the D + Q‐induced transcriptomic responses in tree shrews exhibited markedly greater concordance with human aging signatures than did corresponding mouse datasets. Collectively, these findings establish the tree shrew as a translationally relevant aging model that bridges the gap between fundamental discovery and clinical application.
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BibTeX
@article{luo2026tree,
title = {{Tree Shrew as an Emerging Model for Aging Research: Characterization of Senescence and Therapeutic Interventions}},
author = {Qiuni Luo and Wenxian Xiao and Xin Dong and Ayesha Nisar and Yuhua Ma and Xiang Lai and Raoxian Bai and Meiting Zi and Qi Geng and Qingyu Zhang and Cheng Zhang and Qiong Wang and Naheemat Modupeola Gold and Zhen Zhou and Li Hu and Ao Zhang and Qinghua Zeng and Jing Liu and Sawar Khan and Longbao Lv and Yonghan He},
journal = {Aging Cell},
year = {2026},
month = nov,
doi = {10.1111/acel.70781},
url = {https://doi.org/10.1111/acel.70781},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tree Shrew as an Emerging Model for Aging Research: Characterization of Senescence and Therapeutic Interventions
AU - Qiuni Luo
AU - Wenxian Xiao
AU - Xin Dong
AU - Ayesha Nisar
AU - Yuhua Ma
AU - Xiang Lai
AU - Raoxian Bai
AU - Meiting Zi
AU - Qi Geng
AU - Qingyu Zhang
AU - Cheng Zhang
AU - Qiong Wang
AU - Naheemat Modupeola Gold
AU - Zhen Zhou
AU - Li Hu
AU - Ao Zhang
AU - Qinghua Zeng
AU - Jing Liu
AU - Sawar Khan
AU - Longbao Lv
AU - Yonghan He
PY - 2026
DA - 2026/11/03
JO - Aging Cell
DO - 10.1111/acel.70781
UR - https://doi.org/10.1111/acel.70781
AB - Aging is characterized by progressive physiological decline and increased susceptibility to age‐related diseases. Conventional rodent models have contributed significantly to our understanding of aging, yet their translational relevance is limited by substantial evolutionary divergence from humans. Here, we introduce the tree shrew ( Tupaia belangeri chinensis ) as a novel and biologically relevant model organism for aging research. In vitro, we induced cellular senescence in tree shrew fibroblasts through ionizing radiation, doxorubicin treatment, or replicative exhaustion, all of which consistently triggered robust senescent phenotypes and a pronounced senescence‐associated secretory phenotype (SASP), accompanied by upregulation of conserved senescence biomarkers. In vivo, aged tree shrews exhibited progressive physical frailty, metabolic dysfunction, organ fibroplasia, and spontaneous tumorigenesis. Transcriptomic profiling uncovered widespread age‐related alterations across multiple tissues, prominently affecting pathways involved in chronic inflammation, extracellular matrix remodeling, and metabolic dysregulation. Further comparative transcriptomic analyses of liver and spleen tissues confirmed that tree shrews recapitulate conserved human aging transcriptional trajectories and core gene expression patterns, whereas mice displayed markedly divergent aging signatures. Notably, senolytic intervention with dasatinib and quercetin (D + Q) effectively reversed key transcriptional changes and ameliorated selected age‐related pathologies, including hepatic steatosis. Importantly, the D + Q‐induced transcriptomic responses in tree shrews exhibited markedly greater concordance with human aging signatures than did corresponding mouse datasets. Collectively, these findings establish the tree shrew as a translationally relevant aging model that bridges the gap between fundamental discovery and clinical application.
SN - 1474-9718
SN - 1474-9726
ER -