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In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

2016; Cell Press; Volume: 167; Issue: 7 Linguagem: Inglês

10.1016/j.cell.2016.11.052

1097-4172

Alejandro Ocampo, Pradeep Reddy, Paloma Martínez‐Redondo, Aida Platero-Luengo, Fumiyuki Hatanaka, Tomoaki Hishida, Mo Li, David Lam, Masakazu Kurita, Ergin Beyret, Toshikazu Araoka, Eric Vazquez-Ferrer, David A. Donoso, Jose Luis Roman, Jinna Xu, Concepción Rodrı́guez Esteban, Gabriel Núñez, Estrella Núñez‐Delicado, Josep M. Campistol, Isabel Guillen, Pedro Guillén, Juan Carlos Izpisúa Belmonte,

CRISPR and Genetic Engineering

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.