Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism

ABSTRACT: Aging and the chronic diseases associated with aging have become a great burden to modern society. Recent animal studies on heterochronic parabiosis have revealed that young blood has a powerful rejuvenating effect on aged tissues, but which components of the young blood are responsible for the rejuvenating effects remains unclear. In this study, we found that small extracellular vesicles (sEVs) purified from the plasma of young mice could counteract pre-existing aging at the molecular, mitochondrial, cellular and physiological levels. In detail, injection of young sEVs into aged mice extended lifespan, attenuated senescent phenotypes and mitigate age-associated impairments on various tissues (hippocampus, muscle, heart, testis, bone, etc). Mechanistical studies using iTRAQ-based quantitative proteomic analyses combined with GO term cluster revealed that the altered proteomes in aged tissues of young sEVs-treated mice were specifically related to their roles in regulating cellular senescence, metabolic process, epigenetic modification, genomic stability, etc, which are the cardinal features associated with aging. Particularly, the sEVs derived from young mice and young human donors could stimulate PGC-1α (a master regulator of mitochondrial biogenesis and energy metabolism) expression in vitro and in vivo through their rejuvenating miRNA cargos, thereby facilitating mitochondrial regeneration and counteracting mitochondrial deficits in aged tissues. Taken together, this study demonstrates that young sEVs can reverse degenerative changes and age-related dysfunctions through stimulating PGC-1α expression and regenerating intact mitochondria.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, Heart, Testis, Brain, Skeletal Muscle, Lung, Liver, Kidney

SUBMITTER: Jingzi Zhang  

LAB HEAD: Chen Xi

PROVIDER: PXD030350 | Pride | 2024-03-31

REPOSITORIES: Pride