In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

被引：621

作者：

Ocampo, Alejandro ^{[1
]}

Reddy, Pradeep ^{[1
]}

Martinez-Redondo, Paloma ^{[1
]}

Platero-Luengo, Aida ^{[1
]}

Hatanaka, Fumiyuki ^{[1
]}

Hishida, Tomoaki ^{[1
]}

Li, Mo ^{[1
]}

Lam, David ^{[1
]}

Kurita, Masakazu ^{[1
,2
]}

Beyret, Ergin ^{[1
]}

Araoka, Toshikazu ^{[1
,2
]}

Vazquez-Ferrer, Eric ^{[1
]}

Donoso, David ^{[1
]}

Roman, Jose Luis ^{[1
]}

Xu, Jinna ^{[1
]}

Esteban, Concepcion Rodriguez ^{[1
]}

Nunez, Gabriel ^{[3
,4
]}

Nunez Delicado, Estrella ^{[2
]}

Campistol, Josep M. ^{[5
]}

Guillen, Isabel ^{[6
]}

Guillen, Pedro ^{[6
]}

Belmonte, Juan Carlos Izpisua ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA

[2] Universidad Catolica San Antonio Murcia UCAM, Campus Jeronimos, Murcia 30107, Spain

[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[5] Univ Barcelona, Hosp Clin, IDIBAPS, E-08036 Barcelona, Spain

[6] Fdn Dr Pedro Guillen, Clin Cemtro, Madrid 28035, Spain

来源：

CELL | 2016年 / 167卷 / 07期

关键词：

BETA-CELL PROLIFERATION; SOMATIC-CELLS; EPIGENETIC REGULATION; QUIESCENCE; REJUVENATION; FIBROBLASTS; METABOLISM; MECHANISMS; CONVERSION; SENESCENT;

D O I：

10.1016/j.cell.2016.11.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mousemodel 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.

引用

页码：1719 / +

页数：27

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