Perspectives to Modify and Counter Aging in the Frame of Subtelomere–Telomere Theory of Aging

Abstract

The interpretation of aging as an adaptive and programmed phenomenon implies the existence of specific genetically determined and regulated aging-causing mechanisms. This interpretation is in contrast to the explanation of aging as the gradual accumulation of the effects of harmful factors that are only partially countered by natural selection. The subtelomere–telomere theory of aging offers what is required by the interpretation of aging as a programmed phenomenon. The experimentally documented mechanisms that are part of the subtelomere–telomere theory are the repression of subtelomeric sequences (TERRA sequences) consequent to the sliding of a telomeric hood over subtelomere in proportion to telomere shortening, epigenetic modifications caused by the repression of the subtelomeric sequences, cell senescence and gradual cell senescence (which are not synonyms, as discussed in the text), progressive decline of stem cells, and effects of these phenomena over the whole organism. Evidence against the interpretation of cell senescence and telomerase restrictions as defense mechanisms against cancer is reported. Consequently, the fears that telomerase activation or senescent cell elimination are potentially oncogenic factors should be eliminated as preconceived ideas or limited on the basis of any available evidence. In the context of the mechanisms described under the subtelomere–telomere theory, three types of strategies that could be used to modify and counter the mechanisms of aging can be deduced, namely telomerase activation, senescent cell elimination, and restoration of stem cell numbers to that existing in young individuals. The limits and the potential effectiveness of these methods, already the subject of active research, are briefly discussed.