TY - JOUR

T1 - Age reprogramming and epigenetic rejuvenation

AU - Singh, Prim B.

AU - Newman, Andrew G.

PY - 2018/12/20

Y1 - 2018/12/20

N2 - Age reprogramming represents a novel method for generating patient-specific tissues for transplantation. It bypasses the de-differentiation/redifferentiation cycle that is characteristic of the induced pluripotent stem (iPS) and nuclear transfer-embryonic stem (NT-ES) cell technologies that drive current interest in regenerative medicine. Despite the obvious potential of iPS and NT-ES cell-based therapies, there are several problems that must be overcome before these therapies are safe and routine. As an alternative, age reprogramming aims to rejuvenate the specialized functions of an old cell without de-differentiation; age reprogramming does not require developmental reprogramming through an embryonic stage, unlike the iPS and NT-ES cell-based therapies. Tests of age reprogramming have largely focused on one aspect, the epigenome. Epigenetic rejuvenation has been achieved in vitro in the absence of de-differentiation using iPS cell reprogramming factors. Studies on the dynamics of epigenetic age (eAge) reprogramming have demonstrated that the separation of eAge from developmental reprogramming can be explained largely by their different kinetics. Age reprogramming has also been achieved in vivo and shown to increase lifespan in a premature ageing mouse model. We conclude that age and developmental reprogramming can be disentangled and regulated independently in vitro and in vivo.

AB - Age reprogramming represents a novel method for generating patient-specific tissues for transplantation. It bypasses the de-differentiation/redifferentiation cycle that is characteristic of the induced pluripotent stem (iPS) and nuclear transfer-embryonic stem (NT-ES) cell technologies that drive current interest in regenerative medicine. Despite the obvious potential of iPS and NT-ES cell-based therapies, there are several problems that must be overcome before these therapies are safe and routine. As an alternative, age reprogramming aims to rejuvenate the specialized functions of an old cell without de-differentiation; age reprogramming does not require developmental reprogramming through an embryonic stage, unlike the iPS and NT-ES cell-based therapies. Tests of age reprogramming have largely focused on one aspect, the epigenome. Epigenetic rejuvenation has been achieved in vitro in the absence of de-differentiation using iPS cell reprogramming factors. Studies on the dynamics of epigenetic age (eAge) reprogramming have demonstrated that the separation of eAge from developmental reprogramming can be explained largely by their different kinetics. Age reprogramming has also been achieved in vivo and shown to increase lifespan in a premature ageing mouse model. We conclude that age and developmental reprogramming can be disentangled and regulated independently in vitro and in vivo.

KW - Age reprogramming

KW - eAge

KW - Epigenetic clock

KW - Epigenetic rejuvenation

KW - iPS cells

KW - Reprogramming factors

KW - Somatic cell nuclear transfer (SCNT)

KW - Epigenomics

KW - Age Factors

KW - Humans

KW - Cellular Reprogramming/physiology

KW - Nuclear Transfer Techniques

KW - Induced Pluripotent Stem Cells/physiology

KW - Aging/physiology

KW - Animals

KW - Stem Cell Transplantation/methods

KW - Cell Differentiation

KW - Embryonic Stem Cells/physiology

KW - Pluripotent Stem Cells/physiology

KW - Regenerative Medicine/methods

KW - Epigenesis, Genetic/genetics

KW - Rejuvenation/physiology

KW - HALLMARKS

KW - CELLS

KW - SENESCENT

UR - http://www.scopus.com/inward/record.url?scp=85058885318&partnerID=8YFLogxK

U2 - 10.1186/s13072-018-0244-7

DO - 10.1186/s13072-018-0244-7

M3 - Review article

C2 - 30572909

AN - SCOPUS:85058885318

VL - 11

SP - 73

JO - Epigenetics and Chromatin

JF - Epigenetics and Chromatin

SN - 1756-8935

IS - 1

M1 - 73

ER -