Arguments against telomere-telomerase system
as general defence against cancer
Independent researcher, Naples, Italy
Telomere-telomerase system, which is genetically determined and regulated, causes cell senescence and limits cell replication capacity. The existence of life-limiting mechanisms is specifically predicted by adaptive aging theories while the contrary is true for non-adaptive aging theories. Therefore, for this second type of theories, it is essential an adaptive function to justify the existence of these life-limiting mechanisms.
A popular interpretation is that they are a general defence against cancer but there are strong arguments against this hypothesis:
1) It does not justify: a) the existence of animals that show in the wild no observable increase in age-specific mortality rate, cancer mortality included; b) the great differences of duplication limits and of cell overall functionality decay from species to species, unless cancer risk is postulated as varying from species to species in direct correlation with the limits imposed to cell duplication capacities and to cell overall functionality by the genetic modulation of telomere-telomerase system;
2) Shortened telomeres increase vulnerability to cancer as a consequence of dysfunctional telomere-induced instability;
3) The decline of duplication capacities and of overall cell functionality weakens immune system efficiency, which is inversely related to cancer incidence;
4) The role of the telomere in chromosomal stability argues that telomerase protects against carcinogenesis.
5) In yeast, an eukaryotic species, replicative senescence and cell senescence, although not caused by telomere shortening but by another mechanism related to the number of duplications, cannot be a consequence of an impossible cancer risk. Moreover, these phenomena and others strictly associated observed in yeast have been interpreted as adaptive.
6) Dyskeratosis congenita, an inherited human disease, is characterized by an altered telomerase. Problems tend to occur in tissues in which cells multiply rapidly and there is a higher rate of cancer that can likewise be explained by the lack of telomerase, which results in unstable chromosomes.
But: 7) in rodents, telomerase activity is not related to maximum lifespan while is inversely related to body mass and this has been interpreted as a fact in support of the defensive role against cancer risk of telomere-telomerase system, as a greater body mass presumably increases cancer risk.
In short, with the important exception of point (7), which stimulates further data and discussions, there are not specific arguments and experimental tests in support of the hypothesis that telomere-telomerase age-related limiting actions on cell turnover is a general defence against cancer. Therefore, telomere-telomerase age-related limits on cell turnover are hardly justifiable as a defence against cancer risk and, lacking other plausible explanations, only the adaptive hypotheses of age-related fitness decline appear a rational cause for their existence.
Homo Sapiens Liberatus Workshop, Moscow State University, May 2010