In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

Alejandro Ocampo, Pradeep Reddy, Paloma Martinez-Redondo, Aida Platero-Luengo, Fumiyuki Hatanaka, Tomoaki Hishida, Mo Li, David Lam, Masakazu Kurita, Ergin Beyret, Toshikazu Araoka, Eric Vazquez-Ferrer, David Donoso, Jose Luis Roman, Jinna Xu, Concepcion Rodriguez Esteban, Gabriel Nuñez, Estrella Nuñez Delicado, Josep M. Campistol, Isabel GuillenPedro Guillen, Juan Carlos Izpisua Belmonte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

221 Scopus citations

Abstract

Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.

Original languageEnglish (US)
Pages (from-to)1719-1733.e12
JournalCell
Volume167
Issue number7
DOIs
StatePublished - Dec 15 2016

Keywords

  • aging
  • cellular reprogramming
  • epigenetics
  • lifespan

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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