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By controlling the growth of telomeres, it may eventually be possible to coax healthy cells to keep dividing and generating even in old age.
The cells in our bodies are constantly dividing, replenishing our lungs, skin, liver, and other organs. Regrettably, most human cells can't keep on dividing forever. Each time a cell divides, a cellular "timekeeper" at the ends of the chromosomes shortens. These timekeepers, called telomeres, are like the aglets at the end of your shoelaces — those important bits of plastic that prevent the lace ends from fraying. But in the case of shortened telomeres, cells are no longer able to divide, resulting in a host of aging-related complications, including organ and tissue degeneration.
Patching the Ends
Back in 1973, Soviet biologist Alexey Olovnikov predicted the existence of a "fix" or compensatory mechanism for this process. Scientists Carol Greider and Elizabeth Blackburn were awarded the Nobel Prize in 1984 by proving him right. Their team discovered that some cells produce an enzyme called telomerase, which rebuilds telomeres and allows cells to divide indefinitely. This enzyme — which carries its own template (in the form of an RNA molecule) to elongate the telomeres — adds DNA sequence repeats to the end of DNA strands in the telomere regions. Think of them as disposable buffers that block the ends of chromosomes.
Aging, therefore, was thought to arise from a lack of telomerase — but it now appears that telomerase activity is a bit more complicated than that.
The new research shows that telomerase has a kind of toggle switch, and if the switch happens to be flipped to the "off" position, merely having adequate levels of telomerase in our cells may simply not be enough. The research team of Vicki Lundblad and Timothy Tucey discovered that telomerase — even when present — can be turned off, or disassembled. That's a huge deal because an understanding of how this "off" switch can be manipulated — thereby slowing down the telomere shortening process — could eventually lead to treatments for an assortment of aging-related diseases. For example, the regeneration of vital organs later in life.
Lundblad and Tucey made the discovery while working with the yeast Saccharomyces cerevisiae, the same yeast used to make wine and bread. The team developed a strategy that allowed them to observe each component during cell growth and division at very high resolution. This led to an unexpected series of discoveries into how — and when — the telomerase complex puts itself together.
A release from the Salk Institute explains:
Every time a cell divides, its entire genome must be duplicated. While this duplication is going on, Tucey discovered that telomerase sits poised as a "preassembly" complex, missing a critical molecular subunit. But when the genome has been fully duplicated, the missing subunit joins its companions to form a complete, fully active telomerase complex, at which point telomerase can replenish the ends of eroding chromosomes and ensure robust cell division.
Surprisingly, however, Tucey and Lundblad showed that immediately after the full telomerase complex has been assembled, it rapidly disassembles to form an inactive "disassembly" complex — essentially flipping the switch into the "off" position. They speculate that this disassembly pathway may provide a means of keeping telomerase at exceptionally low levels inside the cell.
The Cancer Connection
Eroding telomeres in normal cells contribute to the aging process, but cancer cells depend on elevated telomerase levels to ensure unregulated cell growth. As explained by the University of Utah's Genetic Science Learning Center:
As a cell begins to become cancerous, it divides more often, and its telomeres become very short. If its telomeres get too short, the cell may die. Often times, these cells escape death by making more telomerase enzyme, which prevents the telomeres from getting even shorter.
Many cancers have shortened telomeres, including pancreatic, bone, prostate, bladder, lung, kidney, and head and neck.
Measuring telomerase may be a way to detect cancer. And if scientists can learn how to stop telomerase, they might be able to fight cancer by making cancer cells age and die. In one experiment, researchers blocked telomerase activity in human breast and prostate cancer cells growing in the laboratory, prompting the tumor cells to die. But there are risks. Blocking telomerase could impair fertility, wound healing, and production of blood cells and immune system cells.
Remarkably, Tucey's and Lundblad's "off switch" could be used to keep telomerase activity below the critical threshold. But as noted, the introduction of a potential anti-aging maintenance protocol, while beneficial for some therapies, could prove detrimental to others. Clearly, we're still far from anything even remotely approximating human trials (we are talking about yeast cells, after all), but the fact that scientists can now control the growth of telomeres is pretty damned exciting.
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