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Review
. 2014 Feb;13(1):2-7.
doi: 10.1111/acel.12182. Epub 2013 Nov 21.

The Aging Signature: A Hallmark of Induced Pluripotent Stem Cells?

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Free PMC article
Review

The Aging Signature: A Hallmark of Induced Pluripotent Stem Cells?

Leili Rohani et al. Aging Cell. .
Free PMC article

Abstract

The discovery that somatic cells can be induced into a pluripotent state by the expression of reprogramming factors has enormous potential for therapeutics and human disease modeling. With regard to aging and rejuvenation, the reprogramming process resets an aged, somatic cell to a more youthful state, elongating telomeres, rearranging the mitochondrial network, reducing oxidative stress, restoring pluripotency, and making numerous other alterations. The extent to which induced pluripotent stem cell (iPSC)s mime embryonic stem cells is controversial, however, as iPSCs have been shown to harbor an epigenetic memory characteristic of their tissue of origin which may impact their differentiation potential. Furthermore, there are contentious data regarding the extent to which telomeres are elongated, telomerase activity is reconstituted, and mitochondria are reorganized in iPSCs. Although several groups have reported that reprogramming efficiency declines with age and is inhibited by genes upregulated with age, others have successfully generated iPSCs from senescent and centenarian cells. Mixed findings have also been published regarding whether somatic cells generated from iPSCs are subject to premature senescence. Defects such as these would hinder the clinical application of iPSCs, and as such, more comprehensive testing of iPSCs and their potential aging signature should be conducted.

Keywords: aging; differentiation; epigenetic; induced pluripotent stem; reprogramming; telomeres.

Figures

Figure 1
Figure 1
Epigenetic memory and reprogramming. There are controversial data regarding the epigenetic memory of induced pluripotent stem cell (iPSC)s and whether or not this memory affects the differentiation potential of reprogrammed cells. iPS cells have been reported to feature incomplete epigenetic reprogramming compared to ESCs, retaining residual methylation signatures characteristic of their tissue of origin that favor differentiation into lineages related to the donor cell.
Figure 2
Figure 2
Aspects of aging and reprogramming. There are currently conflicting data regarding the ability of reprogramming to fully rejuvenate an aged somatic cell and reverse age-related changes such as DNA damage, shortened telomeres, and dysfunctional mitochondria. Moreover, contentious data exist suggesting that cells derived from induced pluripotent stem cells may be subject to premature senescence.

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