Fight Aging!

Telomeres are the protective caps of material at the ends of your chromosomes. As normal somatic cells divide, telomeres become shorter and shorter until the lack of telomere length halts the cell division process - in effect this limits normal cellular replication. But stem cells, the source of our tissues during growth and maintainers of adult tissue, use the enzyme telomerase to keep their telomeres long, enabling them to divide long past the point at which somatic cells would halt. In addition, cancers are spawned of mutant cells that hijack this telomerase mechanism in order to multiply rapidly and endlessly.

If we are to engineer an end to aging, we must engineer an end to cancer along the way. I believe that robust cancer therapies based on targeting mechanisms presently under development in the laboratory will be sufficient to this end. Or at least sufficient for long enough to enable far more advanced technologies to be developed. But biomedical gerontologist Aubrey de Grey of the SENS Foundation proposes a more radical and compete solution to the problem of cancer as a part of his Strategies for Engineered Negligible Senescence: whole-body interdiction of lengthening of telomeres, or WILT. In essence, if you remove all possibility of a cell being able to lengthen its telomeres, cancer will never happen. I have posted on the topic of WILT in the past:

This is a very ambitious but potentially far more comprehensive and long-term approach to combating cancer than anything currently available or in development. It is based on the one inescapable vulnerability that all cancer cells share in common: their absolute need to renew their telomeres, the long stretches of gibberish DNA that cap their chromosomes.

One of the many challenges inherent in blocking telomere lengthening is that telomerase is not the only path. There is another method of generating longer telomeres that must also be removed or sabotaged; it is known as alternative lengthening of telomeres, or ALT. I noticed a paper recently that provides a good overview of what is presently known about ALT:

In most human somatic cells, telomerase activity is very low. This leads to gradual telomere shortening which, in turn, can trigger replicative senescence, a process where a cell with critically short telomeres permanently exits from the cycle of division. In contrast, the great majority of cancers are able to maintain their telomere lengths indefinitely. In most cases, this occurs because of an up-regulation of telomerase activity. However, some cancers maintain their telomere lengths through a telomerase-independent process termed alternative lengthening of telomeres (ALT). The telomeres in ALT cells are highly heterogeneous, often extremely long and appear to be maintained through homologous recombination.

Much of what is known about recombinational telomere elongation (RTE) comes from studies in yeast, particularly Saccharomyces cerevisiae and Kluyveromyces lactis. Yeast mutants lacking telomerase undergo growth senescence and most cells eventually die. The cells that survive senescence are found to have lengthened telomeres through a process dependent upon RAD52 and other genes involved in homologous recombination. Recombination in and near telomeres is greatly increased when the telomeres become short. Work in both K. lactis and S. cerevisiae has suggested that RTE lengthens telomeric repeat arrays (Type II RTE) through a "roll and spread" mechanism. According to this model, a small duplex DNA circle consisting of telomeric repeats (t-circle), formed by recombination in cells with critically short telomeres, is used as a template for extending at least one telomere, through a rolling circle copying event. Once one long telomere is formed, other telomeres become extended by copying its sequence.

Interesting, the things that take place in our cells.

Basenko, E., Cesare, A., Iyer, S., Griffith, J., & McEachern, M. (2009). Telomeric circles are abundant in the stn1-M1 mutant that maintains its telomeres through recombination Nucleic Acids Research, 38 (1), 182-189 DOI: 10.1093/nar/gkp814