期刊
AGING CELL
卷 18, 期 1, 页码 -出版社
WILEY
DOI: 10.1111/acel.12877
关键词
aging; aging clock; epigenetic age; iPSC; partial reprogramming; rejuvenation
资金
- cross-council Lifelong Health and Wellbeing Initiative [MR/K026992/1]
- University Of Edinburgh
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Medical Research Council [MC_PC_15075]
- Medical Research Council (Doctoral Training Programme in Precision Medicine)
- University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE) [MR/K026992/1]
- MRC [MC_PC_15075, 1805075] Funding Source: UKRI
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.
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