Epigenetic states can govern the plasticity of a genome to be adaptive to environments
where many stress stimuli and insults compromise the homeostatic system with age.
Although certain elastic power may autonomously reset, reprogram, rejuvenate, or reverse
the organismal aging process, enforced genetic manipulations could at least reset
and reprogram epigenetic states beyond phenotypic plasticity and elasticity in cells,
which can be further manipulated into organisms. The question, however, remains how
we can rejuvenate intrinsic resources and infrastructures in a noninvasive manner,
particularly in a whole complex aging organism. Given inevitable increase of cancer
with age, presumably any failure of resetting, reprogramming, or even rejuvenation
could be a prominent causative factor of malignancy. Accompanied by progressive deteriorations
of physiological functions in organisms with advancing age, aging-associated cancer
risk may essentially arise from unforeseen complications in cellular senescence. At
the cellular level, epithelial-mesenchymal plasticity (dynamic and reversible transitions
between epithelial and mesenchymal phenotypic states) is enabled by underlying shifts
in epigenetic regulation. Thus, the epithelial-mesenchymal transition (EMT) and its
reversal (mesenchymal-epithelial transition [MET]) function as a key of cellular transdifferentiation
programs. On the one hand, the EMT-MET process was initially appreciated in developmental
biology, but is now attracting increasing attention in oncogenesis and senescence,
because the process is involved in the malignant progression vs regression of cancer.
On the other hand, senescence is often considered the antithesis of early development,
but yet between these 2 phenomena, there may be common factors and governing mechanisms
such as the EMT-MET program, to steer toward rejuvenation of the biological aging
system, thereby precisely controlling or avoiding cancer through epigenetic interventions.
Abbreviations:
BMP (bone morphogenetic protein), EMT (epithelial-mesenchymal transition), MET (mesenchymal-epithelial transition), SA-β-gal (senescence β-galactosidase), SASP (senescence-associated secretory phenotype), TGF-β (transforming growth factor β)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: May 21, 2014
Accepted:
May 14,
2014
Received in revised form:
May 9,
2014
Received:
March 6,
2014
Identification
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© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
