Change: A Unified Explanation of Ageing

created on Sept. 1, 2012, 6:14 p.m. by Hevok & updated on Nov. 14, 2012, 10:34 p.m. by Hevok

=============================== A Unified Explanation of Ageing ===============================

:Abstract: Decades of research on the oldest question of mankind, the scientific community was divided by two central dogmas. Once says that ageing is programmed, the other claims ageing is just damage accumulation. However, the truth might be very trivial. Ageing is caused by both by a program and by damage. Hence, in order to reverse ageing, we have to stop this program and to repair the damage. Therefore, we need basic research to illuminate this program and we need SENS, the Strategies for Engineered Negligible Senescence.

To illustrate this, the limits of cell proliferation is clearly programmed, our somatic cells have a determined number of cell duplications they can undergo. This is not just an anti-cancer mechanism; it is to limit our regenerative capacity. Longevity mutants are both protected from cancer and have longer lifespans. Ageing is not just due to a program. I can also hack of one off my arms with a big sharp axe. This is damage, it disables me and it increases my probability to die. Lets assume a lion is attacking me (or a wolf), I cannot defend so properly anymore. I could even crash my teeth with a big hammer. All right, that my teeth are not regrowing is because of a program in my genome. In mice, in contrast, teeth are constantly regrowing. However, this "damage" disables me further, as I cannot anymore eat food efficiently as before and it increases my probability to die just as ageing is doing every day, in the morning, in the evening as well as in the night. Year after year, until I die.

By the way that my arm is not regrowing, is due to a program in my genome, because it has the building blueprint and it did it two times (Yes, I have only two arms. I am not a mutant), the growing thing. Further, several species can regrow appendages, like salamanders. Strangely some of them are stuck in the juvenile state. Maybe I could just induce the gene expression program which is present in my genome, and I could have my arm back again. This would be nice.

The genes in the intersection of juvenile growth, ageing, DR and circadian rhythms which exhibit similar expression patterns (upregulated during juvenile, downregulated in aging and upregulate by DR) are highly coexpressed with mitochondrial and peroxisome genes (i.e. organelles that produce ROS). This fits very well with the ancient metabolic oscillator that is based on ROS oscillations (just as the ultradian oscillation in yeast). The transcription factor ZBTB16, which is know to be highly expressed during gametogenesis, physical interacts with ENOX1. ENOX1 encodes the age-related ENOX protein (arNOX) activity. ENOX proteins connect the ultradian cycle with the circadian oscillations. ENOX protein generate a oscillatory pattern of superoxide with a period length of 26 min that increases linearity with age beginning at about 30 years to a maximum of about age 60 [19734125]. From the age of 30 until advanced old age, there is an exponential increase in the age-specific mortality [Ham and Veomett, 1980].

References

Mechanisms of Development by Richard G. Ham and Marilyn J. Veomett (1980, Hardcover)


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Comment: Minor adjustments.

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