Human iPSCs from aged donors retain their mitochondrial aging signature

Abstract

Aging represents the main risk factor for developing neurodegenerative disorders. One of the hallmarks of aging is mitochondrial dysfunction. Age-related mitochondrial alterations have been shown to affect mitochondrial energy metabolism and redox homeostasis as well as mitochondrial dynamics. In the present study, we addressed the question of whether or not, induced pluripotent stem cells (iPSCs) may be used as a model of "aging in a dish" to identify therapies at alleviating the aging of mitochondria. Notably, we could demonstrate that compared to human iPSCs from young donors, those from aged donors show impaired mitochondrial bioenergetics and exhibit a rise in reactive oxygen species generation. Furthermore, we demonstrate that iPSCs from aged donors present low mitochondrial mass and alterations of the morphology of the mitochondrial network. This study provides evidence that the aging phenotype is present at the mitochondrial level in iPSCs from aged donors, ranging from bioenergetics to dynamics. Thus, this model can be used for high through put screening to identify drugs that improve mitochondrial function. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/589733v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@17c5ccorg.highwire.dtl.DTLVardef@bae9aaorg.highwire.dtl.DTLVardef@142d8e6org.highwire.dtl.DTLVardef@1adf519_HPS_FORMAT_FIGEXP M_FIG C_FIG