Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging

Stefania Petrini, Rossella Borghi, Valentina D'Oria, Fabrizia Restaldi, Sandra Moreno, Antonio Novelli, Enrico Bertini, Claudia Compagnucci

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1453-1469
Number of pages17
JournalAging
Volume9
Issue number5
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Premature Aging
Induced Pluripotent Stem Cells
Nuclear Envelope
Lamin Type A
Cell Aging
Lamin Type B
Progeria
Nuclear Lamina
Intermediate Filaments
Epigenomics
Polymerization
Chromatin
Actins
Protein Isoforms
Down-Regulation

Keywords

  • Actin cytoskeleton
  • Emerin
  • Induced pluripotent stem cells
  • Lamins
  • Mitochondria
  • MKL1
  • Nesprins
  • Nucleoskeleton
  • SIRT7

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

Cite this

Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging. / Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia.

In: Aging, Vol. 9, No. 5, 01.05.2017, p. 1453-1469.

Research output: Contribution to journalArticle

@article{8d24036cba8045408c9375562070b45d,
title = "Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging",
abstract = "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.",
keywords = "Actin cytoskeleton, Emerin, Induced pluripotent stem cells, Lamins, Mitochondria, MKL1, Nesprins, Nucleoskeleton, SIRT7",
author = "Stefania Petrini and Rossella Borghi and Valentina D'Oria and Fabrizia Restaldi and Sandra Moreno and Antonio Novelli and Enrico Bertini and Claudia Compagnucci",
year = "2017",
month = "5",
day = "1",
doi = "10.18632/aging.101248",
language = "English",
volume = "9",
pages = "1453--1469",
journal = "Aging",
issn = "1945-4589",
publisher = "US Administration on Aging",
number = "5",

}

TY - JOUR

T1 - Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging

AU - Petrini, Stefania

AU - Borghi, Rossella

AU - D'Oria, Valentina

AU - Restaldi, Fabrizia

AU - Moreno, Sandra

AU - Novelli, Antonio

AU - Bertini, Enrico

AU - Compagnucci, Claudia

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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.

AB - 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.

KW - Actin cytoskeleton

KW - Emerin

KW - Induced pluripotent stem cells

KW - Lamins

KW - Mitochondria

KW - MKL1

KW - Nesprins

KW - Nucleoskeleton

KW - SIRT7

UR - http://www.scopus.com/inward/record.url?scp=85020080845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020080845&partnerID=8YFLogxK

U2 - 10.18632/aging.101248

DO - 10.18632/aging.101248

M3 - Article

VL - 9

SP - 1453

EP - 1469

JO - Aging

JF - Aging

SN - 1945-4589

IS - 5

ER -