Research Paper Volume 9, Issue 5 pp 1453—1469
Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging
- 1 Confocal Microscopy Core Facility, Research Laboratories, Bambino Gesu' Children's Research Hospital, IRCCS, Rome 00146, Italy
- 2 Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Bambino Gesu' Children's Research Hospital, IRCCS, Rome 00146, Italy
- 3 Department of Science-LIME, University “Roma Tre”, Rome 00146, Italy
- 4 Medical Genetic Unit and Laboratory of Medical Genetics, Bambino Gesu' Children's Research Hospital, IRCCS, Rome, Italy
received: April 27, 2017 ; accepted: May 27, 2017 ; published: May 31, 2017 ;https://doi.org/10.18632/aging.101248
How to Cite
Copyright: Petrini et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.