Ageing as reversible epigenetics?
Increasingly, it's becoming apparent that when cloning an animal, one can reverse most signs of ageing, whilst the integrity of the genome is fully preserved. This reversal process is a subset of epigenetic programming. Consider epigenetics as the metabolic process that governs gene expression. If gene editing and cloning can progress to the extent that ageing reversal can occur in humans, then we've clearly demonstrated that ageing is not a binding or immutable law of nature. Even the very fact that such a possibility exists in principle suggests that ageing is not an inevitable tragedy we must reconcile ourselves with.
This genetic manipulation has not come to fruition yet, so right now, we're mostly reliant on lifestyle choices. However, one central epigenetic process could act as a predictor of mortality risk today - DNA methylation. A methyl group is a configuration of carbon that, via enzymes, can be added onto or removed from DNA to silence or promote gene expression respectively. The pattern of methylation is conserved under cell division, so can be passed down over many generations. In this sense, consider epigenetics as the grease on the wheels of our biological evolution [1].
Methylation occurs at CpG sites, where the cytosine nucleotide links to guanine via a phosphate group. Some resesrchers believe that the methylation pattern at just a few hundred CpG sites (less than 2% of the total) can track our chronological and biological ages well; indeed a more accurate predictor than telomere length. Yet the robustness of these “epigenetic clocks” remains contested and the data is admittedly tenuous, with publication bias potentially distorting findings. Nonetheless, if the latter group is correct, then some modifiable lifestyle choices (such as calorific restriction and inducing autophagy [2]) could decelerate DNA methylation, therefore this process would cause ageing as well as being a symptom of it: an ageing pathway.
Note that, unlike many preposterous claims on this matter, epigenetics does not render our genes redundant. Indeed, epigenetics is still a genetic process. However, it does mean that one cannot easily decompose the effects of genes vs environment.
The paper refers to rapamycin, whose main mechanism for promoting longevity is thought to be via inducing autophagy, via inhibiting the mTOR enzyme that inhibits it.