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 Guillen; Pedro Guillen; Juan Carlos Izpisua Belmonte

doi:10.1016/j.cell.2016.11.052

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 journal › Article › peer-review

555 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 language	English (US)
Pages (from-to)	1719-1733.e12
Journal	Cell
Volume	167
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2016.11.052
State	Published - Dec 15 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

aging
cellular reprogramming
epigenetics
lifespan

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cell.2016.11.052

Cite this

Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., Li, M., Lam, D., Kurita, M., Beyret, E., Araoka, T., Vazquez-Ferrer, E., Donoso, D., Roman, J. L., Xu, J., Rodriguez Esteban, C., Nuñez, G., Nuñez Delicado, E., Campistol, J. M., ... Izpisua Belmonte, J. C. (2016). In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. Cell, 167(7), 1719-1733.e12. https://doi.org/10.1016/j.cell.2016.11.052

@article{dbc52a6181514b77b2aa8ec8ec3b6aee,

title = "In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming",

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",

author = "Alejandro Ocampo and Pradeep Reddy and Paloma Martinez-Redondo and Aida Platero-Luengo and Fumiyuki Hatanaka and Tomoaki Hishida and Mo Li and David Lam and Masakazu Kurita and Ergin Beyret and Toshikazu Araoka and Eric Vazquez-Ferrer and David Donoso and Roman, {Jose Luis} and Jinna Xu and {Rodriguez Esteban}, Concepcion and Gabriel Nu{\~n}ez and {Nu{\~n}ez Delicado}, Estrella and Campistol, {Josep M.} and Isabel Guillen and Pedro Guillen and {Izpisua Belmonte}, {Juan Carlos}",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = dec,

day = "15",

doi = "10.1016/j.cell.2016.11.052",

language = "English (US)",

volume = "167",

pages = "1719--1733.e12",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "7",

}

Ocampo, A, Reddy, P, Martinez-Redondo, P, Platero-Luengo, A, Hatanaka, F, Hishida, T, Li, M, Lam, D, Kurita, M, Beyret, E, Araoka, T, Vazquez-Ferrer, E, Donoso, D, Roman, JL, Xu, J, Rodriguez Esteban, C, Nuñez, G, Nuñez Delicado, E, Campistol, JM, Guillen, I, Guillen, P & Izpisua Belmonte, JC 2016, 'In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming', Cell, vol. 167, no. 7, pp. 1719-1733.e12. https://doi.org/10.1016/j.cell.2016.11.052

TY - JOUR

T1 - In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

AU - Ocampo, Alejandro

AU - Reddy, Pradeep

AU - Martinez-Redondo, Paloma

AU - Platero-Luengo, Aida

AU - Hatanaka, Fumiyuki

AU - Hishida, Tomoaki

AU - Li, Mo

AU - Lam, David

AU - Kurita, Masakazu

AU - Beyret, Ergin

AU - Araoka, Toshikazu

AU - Vazquez-Ferrer, Eric

AU - Donoso, David

AU - Roman, Jose Luis

AU - Xu, Jinna

AU - Rodriguez Esteban, Concepcion

AU - Nuñez, Gabriel

AU - Nuñez Delicado, Estrella

AU - Campistol, Josep M.

AU - Guillen, Isabel

AU - Guillen, Pedro

AU - Izpisua Belmonte, Juan Carlos

PY - 2016/12/15

Y1 - 2016/12/15

N2 - 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.

AB - 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.

KW - aging

KW - cellular reprogramming

KW - epigenetics

KW - lifespan

UR - http://www.scopus.com/inward/record.url?scp=85006243183&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2016.11.052

DO - 10.1016/j.cell.2016.11.052

M3 - Article

C2 - 27984723

AN - SCOPUS:85006243183

SN - 0092-8674

VL - 167

SP - 1719-1733.e12

JO - Cell

JF - Cell

IS - 7

ER -

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this