Telomere Length and Aging



Advocates of human life extension promote the idea of lengthening the telomeres in certain cells through temporary activation of telomerase (by drugs), or possibly permanently by gene therapy. They reason that this would extend human life. So far these ideas have not been proven in humans.

However, it has been hypothesized that there is a trade-off between cancerous tumor suppression and tissue repair capacity, in that lengthening telomeres might slow aging and in exchange increase vulnerability to cancer (Weinstein and Ciszek, 2002).

A study done with the nematode worm species Caenorhabditis elegans indicates that there is a correlation between lengthening telomeres and a longer lifespan. Two groups of worms were studied which differed in the amount of the protein HRP-1 their cells produced, resulting in telomere lengthening in the mutant worms. The worms with the longer telomeres lived 24 days on average, about 20 percent longer than the normal worms.(Joeng et al., 2004).

Techniques to extend telomeres could be useful for tissue engineering, because they might permit healthy, noncancerous mammalian cells to be cultured in amounts large enough to be engineering materials for biomedical repairs.

Occasionally, the telomeres in a clone's DNA are longer because they get "reprogrammed". The clone's new telomeres combine with the old ones, giving it abnormally long telomeres.

Sierra Sciences, a biotechnology company in Reno, NV, has discovered a small-molecule, drug-like compound that turns on the expression of telomerase in human cells. Their scientists are presently characterizing its mechanism of action.

Telomere Length Assay

Several techniques are currently employed to assess average telomere length in eukaryotic cells. The most widely used method is the Terminal Restriction Fragment (TRF) southern blot which involves hybridization of a radioactive 32P-(TTAGGG)n oligonucleotide probe to Hinf / Rsa I digested genomic DNA embedded on a nylon membrane; and subsequently exposed to autoradiographic film or phosphoimager screen. Another histochemical method, termed Q-FISH, involves fluorescent in situ hybridization (FISH). Q-FISH, however, requires significant amounts of genomic DNA (2-20 micrograms) and labor which renders its use limited in large epidemiological studies. Some of these impediments have been overcome with a Real-Time PCR assay for telomere length and Flow-FISH. RT-PCR assay involves determining the Telomere-to-Single Copy Gene (T/S)ratio which is demonstrated to be proportional to the average telomere length in a cell. The Real-Time PCR assay has been since scaled up to high-throughput 384-well format use; making the assay feasible for use in large cohort studies. Flow-FISH is an adaptation of the Q-FISH telomere quantitation technique that uses a flow cytometer to measure median fluorescence of a population of cells, thus reducing labor requirements and increasing reproducibility. Flow-FISH has been scaled up to the 96-well format.

(Baerlocher GM, Vulto I, de Jong G, Lansdorp PM. Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nat Protoc 2006; 1:2365–2376.)


The enzyme telomerase allows for replacement of short bits of DNA known as a telomere, which are otherwise lost when a cell divides via mitosis.

In normal circumstances, without the presence of telomerase, if a cell divides recursively, at some point all the progeny will reach their Hayflick limit. With the presence of telomerase, each dividing cell can replace the lost bit of DNA, and any single cell can then divide unbounded. While this unbounded growth property has excited many researchers, caution is warranted in exploiting this property, as exactly this same unbounded growth is a crucial step in enabling cancerous growth.

Embryonic stem cells express telomerase, which allows them to divide repeatedly and form the individual. In adults, telomerase is expressed in cells that need to divide regularly (e.g., in the immune system), although most somatic cells do not express it.

A variety of premature aging syndromes are associated with short telomeres.[4] These include Werner syndrome, Ataxia telangiectasia, Bloom syndrome, Fanconi anemia, Nijmegen breakage syndrome, and ataxia telangiectasia-like disorder. The genes that have been mutated in these diseases all have roles in the repair of DNA damage, and their precise roles in maintaining telomere length are an active area of investigation. While it is currently unknown to what extent telomere erosion contributes to the normal aging process, maintenance of DNA in general, and telomeric DNA specifically , have emerged as major players. Dr. Michael Fossel has suggested in an interview that telomerase therapies may be used not only to combat cancer but also to actually get around human aging and extend lifespan significantly. He believes human trials of telomerase-based therapies for extending lifespan will occur within the next 10 years. This timeline is significant because it coincides with the retirement of Baby Boomers in the United States and Europe.

Despite the blatant involvement of telomerase dysfunction in specific genetic pathologies, the link between telomere dysfunction and aging is, at present, profoundly speculative. Telomere shortening may very well have absolutely no role in the etiology of the aging process, and more research is needed to discern whether or not this is the case. In particular, recent research has called into the question the role of telomeres as "cellular clocks" shortening with each division, due to the role of telomeres in mediating other cellular damage processes. Additionally, there is evidence that post-mitotic cells such as neurons undergo cellular aging, yet mitosis-mediated telomere-shortening having a role in this is extraordinarily dubious because these differentiated cells do not divide. Furthermore, even if telomeres were demonstrated to have a role in cellular aging, this does not necessarily translate into anything relevant for the treatment or reversal of organismal aging.


Lately the role of telomeres in cellular senescence has aroused general interest, especially with a view to the possible genetically adverse effects of cloning. The successive shortening of the chromosomal telomeres with each cell cycle is also believed to limit the number of divisions of the cell, thus contributing to aging. There have, on the other hand, also been reports that cloning could alter the shortening of telomeres. Some cells do not age and are therefore described as being "biologically immortal." It is theorized by some that when it is discovered exactly what allows these cells, whether it be the result of telomere lengthening or not, to divide without limit that it will be possible to genetically alter other cells to have the same capability. It is further theorized that it will eventually be possible to genetically engineer all cells in the human body to have this capability by employing gene therapy and thereby stop or reverse aging, effectively making the entire organism potentially immortal.

(Hanahan D, Weinberg RA (2000). "The hallmarks of cancer". Cell 100 (1): 57–70)


In humans and other animals, cellular senescence has been attributed to the shortening of telomeres with each cell cycle; when telomeres become too short, the cells die. The length of telomeres is therefore the "molecular clock," predicted by Hayflick. Telomere length is maintained in immortal cells (e.g. germ cells and keratinocyte stem cells, but not other skin cell types) by the enzyme telomerase. In the laboratory, mortal cell lines can be immortalized by the activation of their telomerase gene, present in all cells but active in few cell types. Cancerous cells must become immortal to multiply without limit. This important step towards carcinogenesis implies, in 85% of cancers, the reactivation of their telomerase gene by mutation. Since this mutation is rare, the telomere "clock" can be seen as a protective mechanism against cancer.

(Hanahan D, Weinberg RA (2000). "The hallmarks of cancer". Cell 100 (1): 57–70)