Very Long-Chain C24:1 Ceramide Is Increased in Serum Extracellular Vesicles with Aging and Can Induce Senescence in Bone-Derived Mesenchymal Stem Cells

Khayrullin, Andrew, Priyanka Krishnan, Luis Martinez-Nater, Bharati Mendhe, Sadanand Fulzele, Yutao Liu, Julie A. Mattison, and Mark W. Hamrick. "Very Long-Chain C24: 1 Ceramide Is Increased in Serum Extracellular Vesicles with Aging and Can Induce Senescence in Bone-Derived Mesenchymal Stem Cells." Cells 8, no. 1 (2019): 37.

Abstract: Extracellular vesicles (EVs), including exosomes and microvesicles, function in cell-to-cell
communication through delivery of proteins, lipids and microRNAs to target cells via endocytosis
and membrane fusion. These vesicles are enriched in ceramide, a sphingolipid associated with the
promotion of cell senescence and apoptosis. We investigated the ceramide profile of serum exosomes
from young (24–40 yrs.) and older (75–90 yrs.) women and young (6–10 yrs.) and older (25–30 yrs.)
rhesus macaques to define the role of circulating ceramides in the aging process. EVs were isolated
using size-exclusion chromatography. Proteomic analysis was used to validate known exosome markers
from Exocarta and nanoparticle tracking analysis used to characterize particle size and concentration.
Specific ceramide species were identified with lipidomic analysis. Results show a significant increase in
the average amount of C24:1 ceramide in EVs from older women (15.4 pmol/sample) compared to
those from younger women (3.8 pmol/sample). Results were similar in non-human primate serum
samples with increased amounts of C24:1 ceramide (9.3 pmol/sample) in older monkeys compared
to the younger monkeys (1.8 pmol/sample). In vitro studies showed that primary bone-derived
mesenchymal stem cells (BMSCs) readily endocytose serum EVs, and serum EVs loaded with C24:1
ceramide can induce BMSC senescence. Elevated ceramide levels have been associated with poor
cardiovascular health and memory impairment in older adults. Our data suggest

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