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Review
. 2024 Feb 28;15(1):1816.
doi: 10.1038/s41467-024-46004-5.

Cellular reprogramming as a tool to model human aging in a dish

Patricia R Pitrez  1   2 , Luis M Monteiro  1   2   3 , Oliver Borgogno  4   5 , Xavier Nissan  6 , Jerome Mertens  7   8 , Lino Ferreira  9   10
Affiliations
Review

Cellular reprogramming as a tool to model human aging in a dish

Patricia R Pitrez et al. Nat Commun. .

Abstract

The design of human model systems is highly relevant to unveil the underlying mechanisms of aging and to provide insights on potential interventions to extend human health and life span. In this perspective, we explore the potential of 2D or 3D culture models comprising human induced pluripotent stem cells and transdifferentiated cells obtained from aged or age-related disorder-affected donors to enhance our understanding of human aging and to catalyze the discovery of anti-aging interventions.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Modeling human aging with iPSCs.
A Strategies to model human aging by (i) inducing aging in iPSC-derived cells, (ii) iPSCs from patients with aging-associated diseases and (iii) premature aging-syndrome iPSCs. B Choices and challenges in the use of iPSCs for human aging modeling.
Fig. 2
Fig. 2. Modeling human aging with direct transdifferentiation of somatic cells.
A Direct transdifferentiation of skin cells (easy available) into somatic cells that are not easy to isolate (e.g. neurons, cardiomyocytes, etc.) can be achieved by reprogramming with cell-specific transcription factors, microRNAs, small molecules, epigenetic regulators, etc. The derived cells can be used for cell therapy, drug screening and disease modeling. B Choices and challenges in the use of transdifferentiated cells for human aging modeling.
Fig. 3
Fig. 3. Modeling human aging with 3D models.
A Creation of 3D aged models by organoids. Initially, iPSCs are differentiated into organoid-initiating cells followed by the culture of these cells in a 3D permissive ECM. B Choices and challenges in the use of 3D models for human aging modeling.
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