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Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity.

ABSTRACT: Induced pluripotent stem cells (IPSCs), with their unlimited regenerative capacity, carry the promise for tissue replacement to counter age-related decline. However, attempts to realize in vivo iPSC have invariably resulted in the formation of teratomas. Partial reprogramming in prematurely aged mice has shown promising results in alleviating age-related symptoms without teratoma formation. Does partial reprogramming lead to rejuvenation (i.e., "younger" cells), rather than dedifferentiation, which bears the risk of cancer? Here, we analyse the dynamics of cellular age during human iPSC reprogramming and find that partial reprogramming leads to a reduction in the epigenetic age of cells. We also find that the loss of somatic gene expression and epigenetic age follows different kinetics, suggesting that they can be uncoupled and there could be a safe window where rejuvenation can be achieved with a minimized risk of cancer.

SUBMITTER: Olova N

PROVIDER: S-EPMC6351826 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity.

Olova Nelly N Simpson Daniel J DJ Marioni Riccardo E RE Chandra Tamir T

Aging cell 20181118 1

Induced pluripotent stem cells (IPSCs), with their unlimited regenerative capacity, carry the promise for tissue replacement to counter age-related decline. However, attempts to realize in vivo iPSC have invariably resulted in the formation of teratomas. Partial reprogramming in prematurely aged mice has shown promising results in alleviating age-related symptoms without teratoma formation. Does partial reprogramming lead to rejuvenation (i.e., "younger" cells), rather than dedifferentiation, wh ...[more]

PMID: 30450724

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