The fact that cancer appears to be the only way that age-related (epi)mutations actually harm our health simplifies matters a great deal: it means that if we can develop a sufficiently-strong rejuvenation biotechnology to protect us from cancer, we will effectively have the (epi)mutation problem licked. In other words: if cancer were completely taken off the table as a cause of age-related ill health, then the impact of (epi)mutations on our lives would be nil, and would continue to be negligible for many decades longer than the current human lifespan.
Fortunately, a strategy to achieve extremely strong protection against cancer does exist, although its implementation is extremely challenging. This strategy is based on the one inescapable vulnerability that all cancer cells share in common: their absolute need to renew their telomeres. Telomeres, as you may know, are long stretches of DNA at the ends of our chromosomes that don’t actually contain any genetic instructions for making proteins, but are instead there to provide a protective “cap” to the rest of the chromosome. In an oft-used metaphor, telomeres act like the nibs that keep the tips of your shoelaces from unraveling, protecting your chromosomes from becoming frayed by metabolic and other damage. But just as shoelace nibs do slowly get worn down over time, so too a cell’s telomeres are worn down a little each time it reproduces itself; and when a cell runs out of telomeres, it quickly self-destructs.
Because cancer cells reproduce at a furious pace, they quickly reach the ends of their telomeric “ropes,” and need to find a way to lengthen them again in order to keep going. Successful cancer cells are the ones that have evolved mutations that exploit one of the cell’s two systems for renewing telomeres: either a primary system called telomerase, or in a few cases an “alternative” system appropriately called Alternative Lengthening of Telomeres (ALT). If a nascent cancer can’t find a way to seize hold of the telomerase-lengthening machinery, their telomeres will run down, their chromosomes will fray, and the cell will be destroyed before it can kill us.
So despite their diversity, all cancer cells share one critical thing in common: they are absolutely dependent for their survival on their ability to hijack telomerase (or, less frequently, ALT). This fact has led the search for drugs that inhibit telomerase activity in cancer cells to become one of the hottest areas of cancer research today.
There is certainly promise in this approach, but the effectiveness of telomerase-inhibiting drugs would be limited by two factors. The first is the fact that some cancers use the ALT mechanism instead of telomerase to keep their telomeres long. Strongly inhibiting telomerase will do nothing to thwart ALT-exploiting cancers – and even in cancers that are initially taking advantage of telomerase, inhibiting the enzyme would still leave ALT in their back pocket.
The second limit on the long-term effectiveness of telomerase-inhibiting drugs is the fact that cancer is an extremely devious disease. Cancer cells are constantly reproducing themselves at a breakneck speed, but their genetic code is wildly unstable, so that novel mutations are constantly appearing in cells within the tumor. As a result, they are continuously throwing out new lines of cancer cells, each of which has a slightly different genetic code and distinct properties. This allows the tumor to harness the power of evolution to overcome drugs and therapies that are thrown at it: while a drug or other therapy may be very effective at killing or disabling the great majority of cells in the tumor, there are usually a few cells lurking somewhere in the tumor with a mutation that allows them to survive the attack. These cells are then able to grow back unimpeded by an otherwise effective-seeming therapy.
This is why so many people with cancer initially respond well to chemotherapy and beat the disease into remission, only to have it come roaring back many months later, in a new form that has evolved resistance to the drug that earlier seemed to defeat it. Through such evolutionary processes, a drug that targets telomerase could seem effective at first, only to be defeated by the cancer cell line if it can (for instance) more effectively break the drug down, or prevent the drug from entering its cells, or put out the biological equivalents of the “chaff” and flares that are used by fighter jets to ward off the targeting systems of hostile missiles. Sooner or later, then, a drug that simply inhibits telomerase activity is likely to stop working.
Researchers should certainly continue researching telomerase-inhibiting drugs, and any that work should be pushed to their limits. But limits there will be.