Fight Aging!

Telomerase is the enzyme responsible for lengthening telomeres, caps of repeating DNA sequences at the end of chromosomes. Telomere length acts as a clock of sorts, as telomeres shorten with each cell division. This is one part of a complicated mechanism that limits the replicative life span of ordinary somatic cells that make up the bulk of tissues, producing the well-known Hayflick limit. Telomerase is active in differerent cell populations to different degrees: in stem cells, for example, it operates to consistently maintain lengthy telomeres, such that the stem cells can renew their own population throughout life, while still periodically creating fresh new batches of somatic cells to replace lost cells in the tissue they support.

Average telomere length is fairly dynamic, depending on the details of tissue maintenance and delivery of fresh cells, and tends to shorten with age and illness. It is most commonly measured in white blood cells, which may have more of a correlation with illness than if measured in other tissues. Telomere length is largely thought of as a marker of age-related damage, not a primary cause of aging, but nonetheless delivery of additional telomerase to mice via genetic engineering has been shown to extend life. It is still an open question as to how exactly this works: slowing the onset of tissue frailty through cell loss is one possibility, but it has been suggested that telomerase may interact with mitochondria in ways that reduce their impact on aging. Mice have quite different telomere dynamics from humans, and delivery of telomerase comes with an associated concern of raised cancer risk: all cancers incorporate mechanisms to keep telomeres long in their cells despite frequent cell divisions.

Here researchers present an interesting new finding about the mechanisms of telomerase, which will no doubt be incorporated into existing initiatives aiming to use telomerase as a way to intervene in the aging process:

In our bodies, newly divided cells constantly replenish lungs, skin, liver and other organs. However, most human cells cannot divide indefinitely - with each division, a cellular timekeeper at the ends of chromosomes shortens. When this timekeeper, called a telomere, becomes too short, cells can no longer divide, causing organs and tissues to degenerate, as often happens in old age. But there is a way around this countdown: some cells produce an enzyme called telomerase, which rebuilds telomeres and allows cells to divide indefinitely.

In a new study [scientists] have discovered that telomerase, even when present, can be turned off. "Previous studies had suggested that once assembled, telomerase is available whenever it is needed. We were surprised to discover instead that telomerase has what is in essence an 'off' switch, whereby it disassembles." Understanding how this "off" switch can be manipulated - thereby slowing down the telomere shortening process - could lead to treatments for diseases of aging (for example, regenerating vital organs later in life).

Every time a cell divides, its entire genome must be duplicated. While this duplication is going on, [researchers] 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, [researchers] 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. Although eroding telomeres in normal cells can contribute to the aging process, cancer cells, in contrast, rely on elevated telomerase levels to ensure unregulated cell growth. The "off" switch [may] help keep telomerase activity below this threshold.

Link: http://www.salk.edu/news/pressrelease_details.php?press_id=2052