In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming
Alejandro Ocampo6, Pradeep Reddy6, Paloma Martinez-Redondo6, 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 Guillen, Pedro Guillen, Juan Carlos Izpisua Belmonte7,
6Co-first author
7Lead Contact
Highlights
• Partial reprogramming erases cellular markers of aging in mouse and human cells
• Induction of OSKM in progeria mice ameliorates signs of aging and extends lifespan
• In vivo reprogramming improves regeneration in 12-month-old wild-type mice
Summary
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.
Keywords: aging, cellular reprogramming, lifespan, epigenetics
Received: August 19, 2016; Received in revised form: October 14, 2016; Accepted: November 28, 2016; Published: December 15, 2016
© 2016 Elsevier Inc.
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