Researchers Discover Off Switch for Ageing Cells

Human chromosomes capped by telomeres (white) / U.S. Department of Energy's Human Genome program via Wikimedia
Janet Fang 24 Sep 2014, 22:55

Researchers have discovered a switch that helps control the growth of telomeres -- the timekeepers of our cells. Flipping the switch could turn off aging cells and encourage healthy ones to keep generating later in life. The study was published in Genes and Development last week.

Each time a cell divides, its entire genome is duplicated. We depend on newly-divided cells to constantly replenish our skin, liver, lungs, and other organs as we age, but most of our cells can’t divide forever. With each division, telomeres shorten. These little caps at the ends of chromosomes affect how quickly our cells age: When they become too short, the cells stop dividing. Recent work suggests that telomere length is associated with human illnesses and even lifespans. 

Some of our cells, however, produce an enzyme called telomerase that rebuilds telomeres. And now, Timothy Tucey and Victoria Lundblad from the Salk Institute reveal that telomerase can be turned off. Understanding how this off switch works means we could someday selectively turn off aging cells and slow down the telomere shortening process, continuing the regeneration of tissue even in old age.

“Previous studies had suggested that once assembled, telomerase is available whenever it is needed,” Lundblad explains in a news release. “We were surprised to discover instead that telomerase has what is in essence an ‘off’ switch, whereby it disassembles.” The enzyme can be present in a cell, but now slow down the cell’s aging. 

The duo examined cell growth and division in a single-celled organism, the yeast Saccharomyces cerevisiae. During the cell’s genome duplication process, telomerase is in its “preassembly complex” mode, where it’s missing one necessary molecular subunit. It’s not until the genome has been duplicated that the missing subunit joins the rest of the subunits to form a complete telomerase complex. That’s when the enzyme replenishes the ends of eroding chromosomes to make sure cell division keeps taking place. 

Immediately after the complete telomerase complex is assembled, they discovered, the whole thing disassembles to form an inactive “disassembly complex," flipping the switch to its off position. 

The team thinks this disassembly pathway helps keep telomerase at low levels inside a cell, since cancer cells rely on elevated telomerase levels for unregulated cell growth.

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