Abstract
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.
Highlights
At present, there is no single, commonly accepted theory of aging
Under conditions of constant exposure to exogenous damaging factors, when metabolism of by-products and endogenous damaging factors are partially or completely impaired, a “shift” toward repair and proliferative processes, or a growth HG (GHG)-shift is required for adequate compensation of functions, which ensures restoration of tissue and function deficiency
A low amplitude and high frequency GHG-shift or regeneration modules can no longer handle adequate quantitative and qualitative replacement of lost tissues and impaired functions. To execute this task in late postnatal ontogenesis, a high amplitude total housekeeping genome (THG) (AHG + GHG)-shift is required, which is typical for early prenatal ontogenesis
Summary
There is no single, commonly accepted theory of aging. All main ideas about the essence of this biological phenomenon can be divided into two large groups. There are two main scientific hypotheses of the understanding of the essence and causes of the aging of multicellular organisms (metazoans)—“initial imperfection” and the existence of an “aging program.”. The role of such a link is claimed by the “inability” of the cell itself to fully restore damage to its genome with aging. This conclusion follows from experimental data (Gorbunova et al, 2007).
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