Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Deconstructing age reprogramming

  • 144 Accesses

  • 1 Citations


It has been proposed that age reprogramming enables old cells to be rejuvenated without passage through an embryonic stage (Singh and Zacouto in J Biosci 35:315–319, 2010). As such, age reprogramming stands apart from the induced pluripotent stem (iPS) and nuclear transfer-embryonic stem (NT-ES) cell therapies where histo-compatible cells are produced only after passage through an embryonic stage. It avoids many of the disadvantages associated with iPS and NT-ES cell therapies. Experimental evidence in support of age reprogramming is burgeoning. Here, we discuss possible new approaches to enhance age reprogramming, which will have considerable benefits for regenerative therapies.

This is a preview of subscription content, log in to check access.

Figure 1
Figure 2
Figure 3


  1. Abad M, Mosteiro L, Pantoja C, Canamero M, Rayon T, Ors I, Grana O, Megias D, Domínguez O, Martínez D, Manzanares M 2013 Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature 502 340–345

  2. Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K, Wang G, Chen J and Ding S 2011 Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat. Cell Biol. 13 215–222

  3. Guo L, Karoubi G, Duchesneau P, Shutova MV, Sung HK, Tonge P, Bear C, Rogers I, Nagy A, Waddell TK 2017 Generation of induced progenitor-like cells from mature epithelial cells using interrupted reprogramming. Stem Cell Rep. 9 1780–1795

  4. Gurdon JB and Melton DA 2008 Nuclear reprogramming in cells. Science 322 1811–1815

  5. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, Deconde R 2013 Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol. Cell 49 359–367

  6. Horvath S 2013 DNA methylation age of human tissues and cell types. Genome Biol. 14 R115

  7. Huh CJ, Zhang B, Victor MB, Dahiya S, Batista LF, Horvath S and Yoo AS 2016 Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts. Elife 5 e18648

  8. Kim Y, Zheng X, Ansari Z, Bunnell MC, Herdy JR, Traxler L, Lee H, Paquola ACM, Blithikioti C, Ku M, Schlachetzki JC 2018 Mitochondrial aging defects emerge in directly reprogrammed human neurons due to their metabolic profile. Cell Rep. 23 2550–2558

  9. Ladewig J, Mertens J, Kesavan J, Doerr J, Poppe D, Glaue F, Herms S, Wernet P, Kögler G, Müller FJ, Koch P 2012 Small molecules enable highly efficient neuronal conversion of human fibroblasts. Nat. Methods 9 575–578

  10. Lapasset L, Milhavet O, Prieur A, Besnard E, Babled A, Ait-Hamou N, Leschik J, Pellestor F Ramirez JM, De Vos J, Lehmann S 2011 Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev. 25 2248–2253

  11. Lopez-Otin C, Blasco MA, Partridge L, Serrano M and Kroemer G 2013 The hallmarks of aging. Cell 153 1194–1217

  12. Manukyan M and Singh PB 2012 Epigenetic rejuvenation. Genes Cells 17 337–343

  13. Manukyan M and Singh PB 2014 Epigenome rejuvenation: HP1beta mobility as a measure of pluripotent and senescent chromatin ground states. Sci. Rep. 4 4789

  14. Mizutani E, Ono T, Li C, Maki-Suetsugu R and Wakayama T 2008 Propagation of senescent mice using nuclear transfer embryonic stem cell lines. Genesis 46 478–483

  15. Nagy A and Nagy K 2010 The mysteries of induced pluripotency: where will they lead? Nat. Methods 7 22–24

  16. Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, Li M, Lam D, Kurita M, Beyret E, Araoka T 2016 In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell 167 1719–1733

  17. Ohnishi K, Semi K, Yamamoto T, Shimizu M, Tanaka A, Mitsunaga K, Okita K, Osafune K, Arioka Y, Maeda T, Soejima H 2014 Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Cell 156 663–677

  18. Ohnuki M, Tanabe K, Sutou K, Teramoto I, Sawamura Y, Narita M, Nakamura M, Tokunaga Y, et al. 2014 Dynamic regulation of human endogenous retroviruses mediates factor-induced reprogramming and differentiation potential. Proc. Natl. Acad. Sci. USA 111 12426–12431

  19. Olova N, Simpson DJ, Marioni RE and Chandra T 2019 Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity. Aging Cell 18 e12877

  20. Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Südhof TC, Wernig M 2011 Induction of human neuronal cells by defined transcription factors. Nature 476 220–223

  21. Sheng C, Jungverdorben J, Wiethoff H, Lin Q, Flitsch LJ, Eckert D, Hebisch M, Fischer J, Kesavan J, Weykopf B, Schneider L 2018 A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation. Nat Commun. 9 4047

  22. Singh PB and Newman A G 2018 Age reprogramming and epigenetic rejuvenation. Epigenet. Chromatin 11 73

  23. Singh PB and Zacouto F 2010 Nuclear reprogramming and epigenetic rejuvenation. J. Biosci. 35 315–319

  24. Tang Y, Liu ML, Zang T and Zhang CL 2017 Direct reprogramming rather than iPSC-based reprogramming maintains aging hallmarks in human motor neurons. Front. Mol. Neurosci. 10 359

  25. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC and Wernig M 2010 Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463 1035–1041

  26. Yamanaka S and Blau HM 2010 Nuclear reprogramming to a pluripotent state by three approaches. Nature 465 704–712

Download references


This work was supported by a grant from the Ministry of Education and Science of Russian Federation #14.Y26.31.0024 and Nazarbayev University (Grant No. 090118FD5311).

Author information

Correspondence to Prim B Singh.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Singh, P.B., Laktionov, P.P. & Newman, A.G. Deconstructing age reprogramming. J Biosci 44, 106 (2019). https://doi.org/10.1007/s12038-019-9923-1

Download citation


  • Age reprogramming
  • Epigenetic rejuvenation
  • iPS cells
  • reprogramming factors
  • Epigenetic clock
  • eAge