There is one such recent study in which the experimenters were not only able to arrest the signs of ageing but ‘reverse’ them! Genetics = cool, alchemy = not so much.
One of the most important instigators of age-related degeneration is progressive damage to the genome. It may be surprising to note that this damage to our DNA happens naturally in our body. Every time a cell divides, a portion of DNA is lost from the chromosomes. This is essentially due to the fact that DNA Polymerases (DNA replicating enzymes) need a template for replication and at the ends of chromosomes no such template is available. Thus, chromosomes ends are lost progressively. Isn’t that dangerous? Yes, it is. However, all chromosomes have non-coding repeats at their ends which protect the coding region in between. These repeats are called ‘telomeres’, and even if telomeres are lost, this coding region (the one coding for the all proteins) is safe. There is, however, a limit to how many telomere repeats you can have and at some point in time, you’re going to run out of telomeres. At this point, the cell has essentially ‘aged’ too much and must leave the cell cycle (this process is called senescence). Multiple such ageing processes, especially in stem cells, are one cause of overall ageing of an organism.
There is an enzyme called ‘telomerase’ which prevents the loss of telomeres. Nevertheless, it isn’t usually active in all cells. The presence of telomerase gives a cell infinite replicative potential, allowing the ‘cell’ to become immortal (which is usually what happens in cancer cells). In the study, what the experimenters did was to create transgenic mice in which they had temporal control over the activation of telomerase in all cells. Their results are fascinating.
Upon these telomerase- deficient mice, the effects of telomerase reactivation were seen. Once the mice were exposed to 4-OHT, it could be seen that the telomeres grew, the cells could re-enter the cell cycle and were no longer senescent. The size of some of the proliferating organs, which had become smaller because of apoptosis, was restored and again, most importantly, the life span of these mice increased. These results suggest that despite the degenerative state of the mice, the reactivation of telomerase could decrease DNA damage and cause the ‘reversal’ of tissue atrophy.
Encouraged by their results the experimenters took it to an even bolder level. Since most age-associated diseases are concerned with the brain, they tried to find out what effect telomerase reactivation would have on the brain. In ageing mammalian brains, an accumulation of DNA damage can be seen and a loss of stem cell proliferation. This could be seen in the telomerase-deficient mice, where their brain size was reduced. Upon telomerase reactivation, telomere elongation could be seen and there was a significant increase in brain size which is an indication that the cells were able to proliferate again. This meant that telomerase reactivation allows the repopulation of brain cells even after a state of degeneration.
Hyposmia, is a condition in which the threshold for detecting odours is decreased. The ability to identify and discriminate between odours is also lessened. It is an age-related disorder in both humans and mice. The processing of ‘smells’ is done in the brain (olfactory neurons). Telomerase-deficient mice showed gross signs of incorrect responses to odours. This, however, was corrected when telomerase was reactivated. The synthesis of neural stem cells which is blocked by telomere loss can be reinitiated with the help of telomerase restoring the ability of mice to distinguish between smells correctly, essentially causing the ‘reversal’ of an age-associated problem.
This unprecedented reversal of age-related decline in the central nervous system, as well as other (especially proliferative) organs was combined with the absence of carcinogenesis. Even with the presence of chromosomal instability, the brief exposure to 4-OHT was insufficient to result in any tumours. Overall, these results sound promising for tissue rejuvenation and prevention of progeroid phenotypes.