Does the length of your telomeres determine the length of your life?
We will explore, but first some necessary background.
Our body is made up of roughly 30 trillion cells which create a diverse range of tissues and organs. Within almost every cell is a structure known as the nucleus which contains 23 pairs of chromosomes.
For a primer on the basics of genetics, see our genetics 101 page.
Each of these chromosomes is made up of millions of “bases” which all together describe our individual genome. The four DNA bases A, T, C and G combine in specific long chains known as genes, which can be read by the cell to produce proteins required for its survival and function.
As you can imagine, the specific DNA code which makes up a gene is very important. When errors are introduced, e.g. a DNA base is changed or missed, the protein coded for by that gene may not be produced at all, may not be as functional, or may act in a completely different way altogether.
When a specific disease arises from one of these changes they are termed “mutations.”
For example, mutations in the TP53 gene are strongly associated with the development of certain types of cancers.
Therefore, protecting our DNA sequence from damage or degradation is of great importance in our cells if we want to stay healthy. Whilst each cell in our body contains numerous mechanisms to prevent DNA damage; today I’m going to talk about the role of a structural feature of our chromosomes, called telomeres, and importantly how they are associated with aging and longevity.
Telomeres play a big role in protecting our DNA as we age.
Telomeres are “helmets” for our DNA
Telomeres are structural ‘caps’ at each end of a chromosome. You can think of them as “helmets” that protect our essential DNA.
Each telomere is comprised of a short repetitive sequence of DNA bases (…TTAGGG…) which is repeated thousands of times. This repetitive sequence doesn’t encode for any genes but has important structural functions including preventing the ends of the chromosomes from fusing with one another, helping to organize the chromosomes in the nucleus of the cell and, importantly, protecting against loss of important DNA sequences required for normal cellular processes. 1
Every time a cell divides, on average, a few hundred bases are lost from the ends of the chromosome as they replicate.
Telomeres form a buffer so we don’t lose “essential DNA.” Because there are thousands of bases of the repetitive telomere sequence, this sequence is lost instead of important DNA sequence encoding genes.
Without telomeres, every time a cell divided, whole genes could be lost, losing critical pieces of the genetic code. When the telomere becomes short enough that a chromosome reaches a ‘critical length’ (where further replication of the cell could result in loss of gene sequence), cell division stops and the cell becomes ‘senescent’ (no longer divides) or undergoes cell death. So it could be said that telomeres provide ‘genomic stability’, 1 but also that their length can be indicative of the relative age of a cell. This is why telomere testing has been equated by many startups as an “age clock” that tells us our true biologic age.
As telomere length is so key in cell survival, a specific enzyme known as ‘telomerase’ exists which functions to maintain telomere length after cell division. Telomerase adds the lost TTAGGG repeat sequence back onto the ends of chromosomes maintaining their length, which is nicely shown in the image below.
Image from Wall Street Journal, U.S. Cell-Aging Researchers Awarded Nobel
However, telomerase is not found in every cell within the body. Rather, it is expressed specifically in germ and stem cells. Germ cells are those that divide to produce gametes (sperm and egg cells) and stem cells are those cells embedded within tissues which divide to replenish and maintain the cell population within the body.
The cells which are produced from stem cell division are termed somatic cells, and they make up the vast majority of cells found within the body. Importantly, telomerase is not expressed in these cells, meaning that telomere shortening will occur eventually leading to the cells becoming senescent or undergoing cell death.
Right now I bet you’re asking, if telomerase is so useful why is it not expressed in every cell? Well, senescence and cell death are key steps in maintaining healthy tissue. Somatic cells are typically highly active and often susceptible to damage and so their ‘death’ and replacement is key in maintaining normal tissue function.
Additionally, regulating telomerase expression is a good way of preventing uncontrolled cell division. A major hallmark of many cancers is expression of telomerase, whereby cells which shouldn’t, are able to divide, uncontrollably, forming tumors. 1 Indeed, several novel anti-cancer therapies are focusing on targeting telomerase activity in order to ‘turn off’ the cancerous cells.
As you can see active telomerase leading to ‘immortal’ cells is not always desirable. But is it possible to draw any conclusions from telomere length and telomerase activity in regards to an individuals health and potential lifespan?
Telomere length and aging
As shortening telomeres beyond a certain ‘critical length’ leads to cell death, the next logical step for researchers was to investigate whether telomeres shorten with increased age of the whole human body.
Most studies measure telomere length in the blood cells, known as leukocytes, or white blood cells, as this is the easiest tissue to get access to via a simple blood sample. The ‘leukocyte telomere length’ (LTL) has also been shown to correlate well with the telomere length in other tissues in the body, meaning the LTL is seen as a good overall indicator of telomere length in an individual as a whole.
There are numerous studies on both sides of the fence debating whether telomere length is significantly associated with mortality and age-related diseases.
Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reported variables. Although telomere length may eventually help scientists understand aging, more powerful and more easily obtained tools are available for predicting survival.
Although telomere length is implicated in cellular aging, the evidence suggesting telomere length is a biomarker of aging in humans is equivocal. More studies examining the relationships between telomere length and mortality and with measures that decline with “normal” aging in community samples are required. These studies would benefit from longitudinal measures of both telomere length and aging-related parameters.
The evidence supporting the hypothesis that telomere length is a biomarker of aging is equivocal, and more data are required from studies that assess telomere length, aging-related functional measures, and collect mortality data. An area for future work is the clarification of which telomere length measure is the most informative and useful marker (e.g., mean, shortest telomere, longitudinal change). Nevertheless, in the near future, longitudinal designs will provide important information about within-individual telomere length dynamics over the life span. Such studies will also elucidate whether the relationships between telomere length and aging-related measures vary across the life span.
Based on the the weak association between telomere length and mortality/age-related diseases discussed above, it may still be a few more years yet before a concrete link is made between SNP data and how long you are likely to live.
But this is cutting edge, exciting science, so expect to see lots of new data soon!
Also, researchers are already developing compounds that are capable of extending telomere length in humans, which may eventually be used to target telomere associated diseases and disorders, or potentially even extend the life of our cells and tissues.
For more on the genetics of telomeres, see our TERT gene page.