Figure 5. Schematic drawing of the age-associated changes occurring in iPSCs following senescence.

Behaviour of nuclear envelope components, mitochondria, actin cytoskeleton and MKL1, NF-kB and SIRT7 in y-iPSCs and their changes following differentiation (differentiated cells) and aging (a-iPSCs). Lamin A appears following cell differentiation whereas its overexpression characterized cell senescence. Augmented levels of prelamin A and progerin are present and widely distributed in nuclear matrix of senescent cells. Lamin B1 is normally polymerized in the nuclear lamina of y-iPSCs and differentiated cells, but reduced in aged cells. Emerin is mildly polymerized and interdispersed around the nuclear rim in colony y-iPSCs, normally distributed upon differentiation, but increased in aged iPSCs. Whereas nesprin-1 is not expressed in iPSCs, nesprin-2 appears following differentiation and increases upon cell aging. Mitochondria are abnormally accumulated in senescent iPSCs, and their distribution seems associated to nucleoskeletal alterations. SIRT7 expression, regulating mitochondrial biogenesis, is reduced in aged iPSCs. Altered nucleo-cytoplasmic MKL1 shuttling, associated with a slow actin polymerization rate that accounts for a decreased dynamism of the cytoskeleton are observed in senescent cells. As inflammatory processes contribute to senescence, NF-kB is hyperactivated by prolonged in vitro culturing (at 21% oxygen).