Research from the laboratory of Professor Julian Chen in the School of Molecular Sciences at Arizona State University recently uncovered a crucial step in the telomerase enzyme catalytic cycle. This catalytic cycle determines the ability of the human telomerase enzyme to synthesize DNA "repeats" (specific DNA segments of six nucleotides) onto chromosome ends, and so afford immortality in cells. Understanding the underlying mechanism of telomerase action offers new avenues toward effective anti-aging therapeutics. illustration depicting the enzyme telomerase This figure depicts the enzyme telomerase as well as telomeres relative to a chromosome. Typical human cells are mortal and cannot forever renew themselves. As demonstrated by Leonard Hayflick a half-century ago, human cells have a limited replicative lifespan, with older cells reaching this limit sooner than younger cells. This "Hayflick limit" of cellular lifespan is directly related to the number of unique DNA repeats found at the ends of the genetic material-bearing chromosomes. These DNA repeats are part of the protective capping structures, termed "telomeres," which safeguard the ends of chromosomes from unwanted and unwarranted DNA rearrangements that destabilize the genome. Each time the cell divides, the telomeric DNA shrinks and will eventually fail to secure the chromosome ends. This continuous reduction of telomere length functions as a "molecular clock" that counts down to the end of cell growth. The diminished ability for cells to grow is strongly associated with the aging process, with the reduced cell population directly contributing to weakness, illness, and organ failure. The fountain of youth at molecular level Counteracting the telomere shrinking process is the enzyme, telomerase, that uniquely holds the key to delaying or even reversing the cellular aging process. Telomerase offsets cellular aging by lengthening the telomeres, adding back lost DNA repeats to add time onto the molecular clock countdown, effectively extending the lifespan of the cell. Telomerase lengthens telomeres by repeatedly synthesizing very short DNA repeats of six nucleotides -- the building blocks of DNA -- with the sequence "GGTTAG" onto the chromosome ends from an RNA template located within the enzyme itself. However, the activity of the telomerase enzyme is insufficient to completely restore the lost telomeric DNA repeats, nor to stop cellular aging.
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