What is a telomere?
Every human cell has 46 chromosomes: 23 from mom and 23 from dad. Each chromosome is DNA library with two tips known as telomeres. All multicellular organisms have telomeres, even plants. In humans and other animals with backbones, they are made of six basepairs, AATCCC on the 5' end matched with TTAGGG. on the 3' end that overhangs and is folded back and protected by protein complexes known as 'shelterin' (see below.) Like aglets on shoelaces, telomeres protect the tips of the chromosome from 'fraying.' Without them, DNA repair enzymes might recognize the tips as breaks that need to be pruned, spliced, or joined.
When any of the 92 telomeres in each cell gets too short, it can rearrange the DNA library ways that cause cellular dysfunction associated with aging. The manifestations of those rearrangements would vary depending on the organ. Severely rearranged chromosomes will be forced into programmed cell death (apoptosis) by watchdog enzymes. Unfortunately, rearrangements at certain oncogenes or tumor suppressor genes can be carcinogenic as illustrated in a well-known cause of leukemia, the Philadelphia Chromosome,
Average telomere lengths shorten with age
At birth, the average human telomere length is 11,000 base pairs. At 20 years, the average is 8,000. By age 50, around 7,000 remain. And so it goes, losing 50-100 base pairs a year until only 4000 remain at age 100.
Note from the slope of the graph that the loss is faster in childhood (when the body is growing) and in old age (when telomerase activation is limited.) interestingly, the greatest rate of loss is from conception until birth, when an entire human is being constructed by intense cellular reproduction and differentiation. The original length of 20,000 is probably established by the egg at conception but drops an amazing 9,000 base pairs to 11,000 at the time of birth
As a Patton Protocol client, you'll learn your telomere length as one of many biomarkers of aging that we monitor with you.
The Hayflick Limit
It was once believed that cell lines were immortal. But to reproduce, each generation of cells needs to unzip and copy all 46 chromosomes, giving each daughter a perfect copy.
Leonard Hayflick discovered that non-stem (i.e. non-telomerase active) cells in a dish can only divide around 60 times before the telomeres become too short to survive. The limit on a cell's maximum lifespan with respect to its descendants is known as its "Hayflick Limit."
Because DNA is unzipped and copied from an original, complimentary strand, any daughter cell's telomeres can't be longer than its mother's and will actually be shortened each division. This is known as ....
Replicative Senescence
DNA can only be synthesized in the 5' to 3' direction. It's just a rule.
In the cartoon above, the red and green master copy of the chromosome's double helix is being unzipped and copied into a light blue daughter copy (the 5' to 3' strand) and the blue-to-yellow 3' to 5' strand. Those newly synthesized strands will combine to form a shorter, daughter copy.
The light blue 5' to 3' copy is made easily because that is the correct and only direction DNA is zipped together. But the blue to yellow 3' to 5' copy made from the original green master (5' to 3') has to be made in 5' to 3' segments with the gaps backfilled in by an enzyme. At the "OOPS!" area above, the 3' to 5' strand is shortened an average of 50-100 basepairs because the end fragment couldn't start copying at very end of the parent's 5' strand.
The daughters' shorter strands will lead to an even shorter copies in the granddaughters. And so on, and so on until the Hayflick Limit comes into play. Clearly, cells freshly-minted from master stem cells with actively-lengthening telomeres are better off than cells born of doomed, telomerase-inactive regular cell lines.
Luckily, the telomeres are like blank tape leaders that don't contain any 'music.' Telomeres are expendable - up to a point. But if any of the 92 telomeres in each cell becomes critically short, bad things start to happen. If we're lucky, the "guardian of the genome," an enzyme named p53, will force rogue cells into apoptosis. If not, a dysfunctional or senescent cell line can become established or worse yet, the line can become malignant.
If a non-stem cell escapes p53 and becomes malignant, it has a good chance to burn out due to the Hayflick limit (assuming it doesn't find a way to activate telomerase.) But if a stem-cell line becomes malignant, the "Cancer Stem Cells" may lead to what we would clinically recognize as cancer. This is another compelling reason to keep the stem cells' telomeres long and healthy.
Telomerase activation allows stem cells to lengthen their telomeres
Stem cells need to reproduce too frequently to survive the Hayflick limit. So they turn on telomerase. Telomerase-active stem cells include some skin cells, intestinal cells, and blood-producing cells. Because the daughters copy the mother's DNA, the daughters won't start life with telomeres longer than their mothers and they will inherit any accumulated DNA transciption errors that occurred in their ancestors. (N.B.: the above cartoon implies the bottom strand is actively lengthened by telomerase. Actually, it should show the top, 3' end being extended as the single strand overhang with the bottom 5' strand being backfilled in with Okazaki fragments.)
Non-stem cells don't activate telomerase
The diagram below shows the purple telomere being extending from its chromosome in the upper left background. The "Active Site" is where the colorful blobs that make up this telomerase enzyme complex (aka 'shelterin') will add the new six base pair repeats TTAGGG over and over again. The green strand is the telomere RNA, which is like the "key" for the ignition of the telomerase engine. 
(source: Podlevsky, J.D., Bley, C.J., Omana, R.V., Qi, X., Chen, J. (2007) The Telomerase Database. Nucleic Acids Res. 36 D339-D343.)
As we would expect, some of the premature aging syndromes (progerias) result from mutations in the telomerase enzyme complex or the blob on the upper right, Dyskerin, which serves as a"keyhole" for the telomerase RNA.
In order to "drive" the telomerase enzyme complex, stem cells have the ability to spice the 3' end of the telomerase RNA (the green strand.)
“We demonstrate that the machinery that removes introns from messenger RNAs also functions in generating the mature 3’ end of the telomerase RNA subunit. It was highly unexpected that the spliceosome could have such a function, as the two steps of removing an internal piece of RNA and gluing the flanking ends together are tightly coupled during intron removal."
(Box et al. "Spliceosomal cleavage generates the 3′ end of telomerase RNA," December 5, 2008; DOI: 10.1038/nature07584)
Non-stem cells may lack the ability to process their telomerase RNA "keys," rendering the "engine" inoperable.
Nanomachines at work - Cajal bodies and PML bodies
Cajal bodies are sites of the aforementioned RNA splicing and are found in rapidly reproducing cells such as stem cells, cancer, and neurons. Those Cajal bodies are sites of telomerase activation and are busy lengthening the shortest of the 92 telomeres in each cell which have become critically short. I love a good analogy and the discoverer of telomerase compares this process to swarming bees.
The "guardian of the genome," p53, is at work in the PML bodies, which are often adjacent to the Cajal bodies. Those nanomachines certainly know what they're doing, even if we do not.
