Recently, a research team led by Professor Wei Tang from the Geriatric Hospital of Nanjing Medical University (NMU), in collaboration with Professor Yunxia Zhu from the School of Basic Medical Sciences, NMU, and Professor Lianju Qin from the Stem Cell Center of the First Affiliated Hospital with NMU, reported a novel intervention strategy for age-related diabetes. The study was published online in Aging Cell, a leading international Q1 journal in aging research, under the title “Small Extracellular Vesicles From Human Amniotic Membrane Mesenchymal Stem Cells Rejuvenate Senescent β Cells and Cure Age-Related Diabetes in Mice”.
Diabetes is a typical age-related metabolic disease. With the accelerating pace of global population aging, the prevalence of type 2 diabetes among elderly individuals continues to rise, making it a major public health challenge that seriously threatens human health. .However, safe and effective intervention strategies that directly target β-cell aging remain limited.
The study systematically demonstrated the critical role of small extracellular vesicles (sEVs) derived from human amniotic membrane mesenchymal stem cells in reversing pancreatic β-cell aging. The researchers found that these sEVs can be efficiently taken up by senescent β cells, markedly improving their functional state, reducing the levels of multiple senescence-associated markers, and suppressing inflammatory responses. Moreover, sEVs treatment restored β-cell identity, and enhanced glucose-stimulated insulin secretion, thereby achieving functional “rejuvenation” of aged β cells at the cellular level.
Using aged diabetic mouse models, this strategy demonstrated pronounced therapeutic efficacy at the organismal level. sEV-based intervention significantly lowered blood glucose levels, improved glucose tolerance and insulin secretion, and promoted the recovery of islet structure and β-cell function. Importantly, no obvious toxic or adverse effects were observed, indicating favorable safety and translational potential. These results suggest that targeting β-cell aging itself may enable disease-modifying intervention for age-related diabetes, rather than being limited to conventional symptomatic glycemic control.
The study, for the first time, proposed and validated the key regulatory axis of “miR-21-5p–IL-6RA–STAT3–MCU”, offering new theoretical insights into the mechanisms underlying the devleopment and progression of age-related diabetes. At the same time, it highlights the unique advantages of stem cell–derived extracellular vesicles as a “cell-free, non-transplantation” intervention strategy in terms of safety and clinical translation, providing a novel and broadly applicable paradigm for precision intervention in aging-related and metabolic diseases.
By addressing cellular senescence as a fundamental biological problem, the study further proposed and validated a novel strategy for pancreatic β-cell functional remodeling. This work not only advances understanding of the pathogenesis of age-related diabetes but also provides a solid foundation for developing precision interventions targeting β-cell aging, with significant scientific value and promising prospects for clinical translation.
Professor Wei Tang (Geriatric Hospital of NMU), Professor Yunxia Zhu (School of Basic Medical Sciences, NMU), and Professor Lianju Qin (the First Affiliated Hospital with NMU) served as co-corresponding authors of the study. Xiao Lei (M.D. candidate, Class of 2022), Zicheng Zhang (M.D. candidate, Class of 2023), and Tong Li (M.Sc. student, Class of 2023) from Nanjing Medical University contributed as co–first authors. This work was supported by Key and General Programs of the National Natural Science Foundation of China, the Jiangsu Provincial Key R&D Program, and the Research Incubation Startup Fund of Jiangsu Province Geriatric Hospital.
The original article link: https://onlinelibrary.wiley.com/doi/10.1111/acel.70327
(Drafted by Professor Yunxia Zhu’s research team; Reviewed by Feng Chen and Juejin Wang; Translation revised by Bei Zhang）
