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INÊS MILAGRE

TITLE

Reprogramming cells to counteract ageing

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ABSTRACT

Ageing is the gradual decline in organismal fitness that occurs over time leading to tissue dysfunction and disease. At the cellular level, ageing is associated with reduced function, altered gene expression and a perturbed epigenome.Induced pluripotent stem cells (iPSCs) can be generated in culture using ectopic expression of only four transcription factors and offer key tissue engineering opportunities and clinical applications, namely, to curb age-related diseases. We have developed the first method, where reprogramming factors are selectively expressed until a rejuvenation point and then withdrawn. We found that cells temporarily lose and then reacquire their cell-of-origin identity. Our method substantially rejuvenated multiple cellular attributes including the transcriptome and the epigenome and, importantly, showed partial functional rejuvenation of skin fibroblasts. Overall, we demonstrate that it is possible to separate rejuvenation from complete pluripotency reprogramming, which should facilitate the discovery of novel anti-ageing strategies.

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