Professor Zhang Chenyu, Professor Chen Xi, Professor Wang Yanbo from the School of Life Sciences, and Professor Fang Lei from the School of Medicine at Nanjing University have revealed a significant discovery: small extracellular vesicles (sEVs) in young blood have the remarkable ability to extend lifespan, restore overall physiological function, and reverse age-related degenerative changes. On April 16, the related research findings were published in Nature Aging.
The Nanjing University research team focused on small extracellular vesicles with a diameter of <200 nanometers and explored their "fountain of youth" effects by repeatedly injecting sEVs from young mice or humans into aged mice. Through in vivo and in vitro models, the study further elucidated the molecular basis of the key role of young sEVs in reversing age-related damage and degenerative changes.
Specifically, sEVs from young plasma combat aging at the molecular, mitochondrial, cellular, and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, alleviates aging phenotypes, and improves the functional decline of multiple age-related tissues. Weekly injections of young sEVs into 20-month-old male mice extended their median lifespan to 1031 days, a 22.7% increase compared to the typical lifespan of 840 days for C57BL/6J male mice. The longest-lived mouse survived for 1266 days, equivalent to 120-130 years in humans. This lifespan extension effect surpasses that of calorie restriction diets, metformin, and nicotinamide.
Quantitative proteomic analysis revealed significant changes in the protein profiles of aged tissues after treatment with young sEVs, which are closely related to metabolic processes. Mechanistically, young sEVs stimulate the expression of PGC-1α, a key regulator of mitochondrial homeostasis, through the miRNA cargo they carry, thereby improving mitochondrial function and alleviating mitochondrial defects in aged tissues both in vitro and in vivo. PGC-1α enhances mitochondrial biogenesis by coordinating the expression of mitochondrial proteins encoded by nuclear and mitochondrial genomes and maintains the stability of mitochondrial quantity and quality by regulating mitochondrial quality control and promoting mitochondrial regeneration.
This study demonstrates that sEVs from young blood counteract aging at the molecular, mitochondrial, cellular, and physiological levels, at least partially through the stimulation of PGC-1α expression and enhancement of mitochondrial energy metabolism to reverse degenerative changes and age-related functional impairments. Importantly, young sEVs, as promising natural carriers, can stably deliver "fountain of youth" factors without toxicity or immunogenicity. Therefore, sEVs can serve as a multifunctional tool to help rejuvenate aging tissues, improve lifelong health, and well-being.
Related paper information: https://doi.org/10.1038/s43587-024-00612-4
