Deregulated mito-nuclear communication alters chromatin plasticity and osteogenic differentiation potential upon ageing in mesenchymal stem cells (MSCs) [ATAC-seq]

We report that upon ageing MSC undergo a metabolic switc, down-regulating glycolysis and inducing fatty acid oxidation, which results in elevated acetyl-CoA levels. However, aged cells exhibit chromatin compaction and histone hypo-aceylation. This is due to the lower levels of citrate carrier, resulting in impaired acetyl-CoA export from mitochondria to the cytosol, which concomitantly affetcs histone acetylation and osteogenesis. Description of aged-associated changes in metabolism, chromatin and stemness using mesenchymal stem cells from isolated from young and old mice.