The metazoan genome composes of sets of housekeeping genes (HG) for fundamental cellular autonomous processes and integrative genes (IntG) that provide integrative functions and form the body as an integrated whole. The main paradigm for multicellularity development which has been improved in evolution, is the submission of the cellular autonomy to the interests of the integrated whole. Permanent increase of the “functional tax” of IntG-genome (IntG-shift) and epigenetic restriction of autonomy in phylogenesis/ontogenesis is the essence and root cause of aging, inherent in the very nature of highly integrated multicellularity. The regulation of the balance shift toward HG can be managed to eliminate aging and avoid carcinogenesis, which is only due to the irreversibility of this shift. Here we propose the criterion for measuring the functional and biological age of cells and the body as a whole for assessing the effectiveness of any type of palliative geroprotective or radical anti-aging intervention.

Background: The mechanisms of the development of cancer in old age and also the mechanisms of aging are not well understood. This paper tries to interpret consequences of malignant tissue transformation from the viewpoint of aging, or in other words, from an insufficient cell adaptation to the needs of repair and proliferation. Subject: A hypothesis is presented that a unified but quite opposite at different stages of ontogenesis mechanism is the basis of atypical growth and embryonic development. In the beginning of a malignant dedifferentiation is an insufficiency of an effective self-renovation and disturbed preservation of its adaptation capability. The suppression of regenerating cell proliferation is the primary event of the development of a dedifferentiated tissue growth. The transformation of normal cells into tumor cells is an adaptive reaction in reply to a shortage of self-regeneration capability and repair. Allowing for the process of rebirth, i.e. the complete restoration of tissues leading to the restrain of senescence proceeds by the type of embryonic growth of tissues, the possibility to use the potential of transformed cells for restraining senescence is proposed. The latter will permit to direct the process of transformation to an integrated growth channel, to prevent the clinical phenomenon of malignancy, and use the potential of transformed cells for realization of the self-renovation program and program of unlimited life duration of the whole organism. Conclusion: By a stimulation or compensation of the age-induced shortage of cell metabolism, two effects can be expected: prevention of cancer and retardation of aging.

Here, we interpret malignant tissue transformation from the aging point of view, that is, as a result of insufficient cell adaptation to the needs of regeneration/repair and proliferation. A consequence of the aging (senescence) process is gradual loss of self-renewal potential. It limits lifespan and leads to death due to the decline of tissue/organ functions, failure of regulatory mechanisms, disruption of endogenous processes and increased susceptibility to exogenous factors. Recapitulation of the embryonic pathway of self-renewal/rejuvenation in adulthood is epigenetically determined. At the postembryonic stage, in the absence of immune privilege, this recapitulation is transformed into cancer (potency expansion of single structures composing the organism to the detriment of the whole organism or disintegrating growth). We suggest that the process of rebirth occurs in the same way as embryonic tissue growth. Thus, the idea to use the potential of the transformed cells to stop the aging process has been proposed.

In the first part of our study, we substantiated that the embryonic reontogenesis and malignant growth (disintegrating growth) pathways are the same, but occur at different stages of ontogenesis, this mechanism is carried out in opposite directions. Cancer has been shown to be epigenetic-blocked redifferentiation and unfinished somatic embryogenesis. We formulated that only this approach of aging elimination has real prospects for a future that is fraught with cancer, as we will be able to convert this risk into a rejuvenation process through the continuous cycling of cell dedifferentiation–differentiation processes (permanent remorphogenesis). Here, we continue to develop the idea of looped ontogenesis and formulate the concept of the rejuvenation circle.

Reversible senescence at the cellular level emerged together with tissue specialization in Metazoans. However, this reversibility (ability to permanently rejuvenate) through recapitulation of early stages of development, was originally a part of ontogenesis, since the pressure of integrativeness was not dominant. The complication of specialization in phylogenesis narrowed this “freedom of maneuver”, gradually “truncating” remorphogenesis to local epimorphosis and further up to the complete disappearance of remorphogenesis from the ontogenesis repertoire. This evolutionary trend transformed cellular senescence into organismal aging and any recapitulation of autonomy into carcinogenesis. The crown of specialization, Homo sapiens, completed this post-unicellular stage of development, while in the genome all the potential for the next stage of development, which can be called the stage of balanced coexistence of autonomous and integrative dominants within a single whole. Here, completing the substantiation of the new section of developmental biology, we propose to call it Developmental Biogerontology.