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REJUVENATION

Dipping a toe in the fountain of youth

Nature Aging volume 2, pages 192–194 (2022)Cite this article

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In cultured cells and in mice with accelerated aging, brief bursts of Yamanaka reprogramming factors reverse some molecular and functional deficits of aging without inducing pluripotency or teratomas. Browder et al. show that partial reprogramming regimens rejuvenate some tissues of physiologically aged mice without overt safety concerns.

The fountain of youth — a mystical source of perpetual rejuvenation — has long motivated human explorers, from the ancient Greeks to Ponce de Leon. Over the past few decades, intrepid scientific explorers have come to a deeper understanding of the genetic and metabolic mechanisms that underlie aging1, rendering the notion of turning back the clock a more plausible prospect. The pioneering work of Shinya Yamanaka established that enforced expression of a core set of transcription factors (OCT4, SOX2, KLF4 and MYC; the Yamanaka factors (YFs))2 could reprogram differentiated somatic cells to pluripotency, effectively reverting cells to their embryonic state and resetting their developmental clock to its very beginning. In this issue of Nature Aging, Browder, Belmonte and colleagues3 demonstrate, in a genetically engineered, physiologically aged mouse model, that partial reprogramming via transient induction of the YFs produces rejuvenating effects in the kidneys and skin, without apparent adverse health effects. These provocative results add to accumulating evidence that suggests the possible therapeutic potential of partial reprogramming to reverse the deleterious effects of aging on tissues, while also unveiling potential limitations that will need to be overcome.

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Fig. 1: Analysis of partial reprogramming protocols as antiaging interventions.

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Authors and Affiliations

  1. Boston Children’s Hospital, Boston, MA, USA

    Arianna Markel & George Q. Daley

  2. Harvard Medical School, Boston, MA, USA

    George Q. Daley

Authors
  1. Arianna Markel
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  2. George Q. Daley
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Correspondence to George Q. Daley.

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Competing interests

A.M. declares no competing interests. G.Q.D. holds a grant from the Milky Way Research Foundation to study partial reprogramming and rejuvenation of tissue function.

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Markel, A., Daley, G.Q. Dipping a toe in the fountain of youth. Nat Aging 2, 192–194 (2022). https://doi.org/10.1038/s43587-022-00188-x

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  • DOI: https://doi.org/10.1038/s43587-022-00188-x

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