1.Nervonic Acid Inhibits Replicative Senescence of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells
Sun Jeong KIM ; Soojin KWON ; Soobeen CHUNG ; Eun Joo LEE ; Sang Eon PARK ; Suk-Joo CHOI ; Soo-Young OH ; Gyu Ha RYU ; Hong Bae JEON ; Jong Wook CHANG
International Journal of Stem Cells 2024;17(1):80-90
Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated β-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence.Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.
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