Tree shrews (Tupaia belangeri chinensis) reproduce human cellular and organ-level aging signatures far more closely than mice, including senescence phenotypes, chronic inflammatory and extracellular matrix pathways, frailty, and spontaneous tumor formation. Senolytic treatment with dasatinib and quercetin reversed key transcriptional changes and reduced hepatic steatosis, with responses more concordant with human aging data than those seen in rodents. The model narrows a long-standing translational gap between preclinical senolytic data and human application.
Key Points
- Tree shrew aging transcriptomes mirror human signatures; mouse signatures diverge markedly
- Dasatinib plus quercetin reversed age-related changes and hepatic steatosis
- Aged tree shrews show frailty, fibrosis, metabolic dysfunction, spontaneous tumors
Longevity Analysis
Senolytic enthusiasm has outpaced the evidence largely because mouse data translate poorly to human physiology; a model whose liver, spleen, and immune-inflammatory aging trajectories track human ones changes the quality of information available before clinical adoption. The pathways flagged here — chronic low-grade inflammation, extracellular matrix remodeling, and metabolic dysregulation in the liver — are the same ones that quietly erode repair capacity, filtering function, and energy output in humans across decades. Clearing senescent cells is an intervention of removal rather than addition, and its value depends on accurate reading of which tissues carry the burden and when.
Original published by Wiley Aging Cell, by Qiuni Luo, Wenxian Xiao, Xin Dong, Ayesha Nisar, Yuhua Ma, Xiang Lai, Raoxian Bai, Meiting Zi, Qi Geng, Qingyu Zhang, Cheng Zhang, Qiong Wang, Naheemat Modupeola Gold, Zhen Zhou, Li Hu, Ao Zhang, Qinghua Zeng, Jing Liu, Sawar Khan, Longbao Lv, Yonghan He .