Int J Stem Cells.  2024 Feb;17(1):80-90. 10.15283/ijsc23101.

Nervonic Acid Inhibits Replicative Senescence of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

• Kim SJ
• Kwon S
• Chung S
• Lee EJ
• Park SE
• Choi SJ
• Oh SY
• Ryu GH
• Jeon HB
• Chang JW

• KMID: 2552020
• DOI: http://doi.org/10.15283/ijsc23101

Abstract

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.

Keyword

Nervonic acid; Replicative senescence; Metabolites; Mesenchymal stem cells