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Cell. 2016 Dec 15;167(7):1719-1733.e12. doi: 10.1016/j.cell.2016.11.052.

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.

Author information

1
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, 30107 Guadalupe, Murcia, Spain.
3
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
4
Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, 30107 Guadalupe, Murcia, Spain.
5
Hospital Clinic, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain.
6
Fundación Dr. Pedro Guillén, Clínica Cemtro, 28035 Madrid, Spain.
7
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: belmonte@salk.edu.

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.

KEYWORDS:

aging; cellular reprogramming; epigenetics; lifespan

PMID:
27984723
PMCID:
PMC5679279
DOI:
10.1016/j.cell.2016.11.052
[Indexed for MEDLINE]
Free PMC Article

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