Telomeres shorten …
A telomere is the end of a chromosome. Telomeres are made of repetitive sequences of non-coding DNA that protect the chromosome from damage. Each time a cell divides, the telomeres become shorter. Eventually, the telomeres become so short that the cell can no longer divide.
The telomere lengths for each one of the percentiles (1-99) in the telomere length distribution of each sample.
The percentages (%) of telomeres of each telomere length (from the shortest to the longest) in the entire distribution.
The percentages (%) of cells with different telomere lengths (from the shortest to the longest) in the entire distribution.
LEARN MORE: Life Length
Telomeres are structures made from DNA sequences and proteins found at the ends of chromosomes. They cap and protect the end of a chromosome like the end of a shoelace. Telomeres limit cellular lifespan and keep cancer growth at bay.
The Hayflick limit, or Hayflick phenomenon, is the number of times a normal human cell population will divide before cell division stops.
The concept of the Hayflick limit was advanced by American anatomist Leonard Hayflick in 1961. Hayflick demonstrated that a normal human fetal cell population will divide between 40 and 60 times in cell culture before entering a senescence phase. This finding refuted the contention by French Nobel laureate Alexis Carrel that normal cells are immortal.
Each time a cell undergoes mitosis, the telomeres on the ends of each chromosome shorten slightly. Cell division will cease once telomeres shorten to a critical length. Hayflick interpreted his discovery to be aging at the cellular level. The aging of cell populations appears to correlate with the overall physical aging of an organism.
The Hayflick limit has been found to correlate with the length of the telomeric region at the end of chromosomes. During the process of DNA replication of a chromosome, small segments of DNA within each telomere are unable to be copied and are lost. This occurs due to the uneven nature of DNA replication, where leading and lagging strands are not replicated symmetrically. The telomeric region of DNA does not code for any protein; it is simply a repeated code on the end region of linear eukaryotic chromosomes. After many divisions, the telomeres reach a critical length and the cell becomes senescent. It is at this point that a cell has reached its Hayflick limit.
Hayflick was the first to report that only cancer cells are immortal. This could not have been demonstrated until he had demonstrated that only normal cells are mortal. Cellular senescence does not occur in most cancer cells due to expression of an enzyme called telomerase. This enzyme extends telomeres, preventing the telomeres of cancer cells from shortening and giving them infinite replicative potential. A proposed treatment for cancer is the usage of telomerase inhibitors that would prevent the restoration of the telomere, allowing the cell to die like other body cells.
Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3′ end of telomeres. A telomere is a region of repetitive sequences at each end of a chromosome. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighboring chromosomes.
Telomerase is a reverse transcriptase enzyme that carries its own RNA molecule (e.g., with the sequence 3′-CCCAAUCCC-5′ in Trypanosoma brucei) which is used as a template when it elongates telomeres. Telomerase is active in gametes and most cancer cells, but is normally absent from, or at very low levels in, most somatic cells.
Telomerase restores short bits of DNA known as telomeres, which are otherwise shortened when a cell divides via mitosis.
In normal circumstances, where telomerase is absent, if a cell divides recursively, at some point the progeny reach their Hayflick limit, which is believed to be between 50–70 cell divisions. At the limit the cells become senescent and cell division stops. Telomerase allows each offspring to replace the lost bit of DNA, allowing the cell line to divide without ever reaching the limit. This same unbounded growth is a feature of cancerous growth.
Some experiments have raised questions on whether telomerase can be used as an anti-aging therapy, namely, the fact that mice with elevated levels of telomerase have higher cancer incidence and hence do not live longer. On the other hand, one study showed that activating telomerase in cancer-resistant mice by over-expressing its catalytic subunit extended lifespan.
A study that focused on Ashkenazi Jews found that long-lived subjects inherited a hyperactive version of telomerase.