Genetics behind ageing probed

Genetic tests to determine how quickly a person will age may soon be available, according to several newspapers. The news is based on the recent discovery of a genetic variation that apparently predisposes some people to faster ageing. The newspapers suggested the research may lead to the easier identification of people at higher risk of age-related illnesses or suggested a possible key to longer lifespan.

Behind these reports is a genome-wide association study that scanned the DNA of several thousand people, identifying a gene variant associated with the length of telomeres - unique sections of DNA that shorten with age. The results suggest the variant is responsible for a small proportion of the variation in telomere length between individuals, equivalent to about 3.6 years of age-related shortening.

This well-conducted research has identified one particular gene variant, but the findings suggest there are many others that also affect the length of telomeres. Much more research will be needed before a practical application aimed at lengthening life would be possible.

Where did the story come from?

The research was carried out by Dr Veryan Codd and colleagues from King’s College, London and other academic institutions across Europe and the UK. The study was funded by the British Heart Foundation and the Wellcome Trust. Individual authors also received grants and financial support from a number of different sources. The study was published in the peer-reviewed medical journal, Nature Genetics .

This discovery was reported by several news sources, all of which highlight the potential of these results to techniques that might identify diseases early or potentially increase lifespan. The Guardian cautions that the results of this study are “unlikely to lead to drugs that dramatically extend lifespan”.

What kind of research was this?

The research was a genome-wide association study looking at whether any particular variant genetic sequences were associated with the length of a person’s telomeres. Telomeres are found at the ends of chromosomes, where they protect the rest of the DNA from damage and deterioration in order to maintain ‘genetic stability’. A genome-wide association study is the best way to assess associations between gene variants and particular characteristics in a large number of people.

The shortening of telomeres (which happens as cells divide) is considered to be a key process in biological ageing - the progressive decline over time in the body’s ability to meet its demands. Biological ageing occurs because cell damage accumulates as a result of environmental and genetic challenges. When the telomere eventually reaches a critically short length, cell death can occur.

This study was specifically looking for variants associated with the length of telomeres in leukocyte white blood cells. The length of leukocyte telomeres has been shown to be associated with the risk of several age-related diseases and has been proposed as a marker of biological ageing.

What did the research involve?

The researchers analysed the DNA of 2,917 individuals, looking for DNA variants known as single nucleotide polymorphisms (SNPs) that were associated with the length of the telomere on a particular chromosome.

The sample population comprised of 1,487 individuals with coronary heart disease taken from a British Heart Foundation study and 1,430 donors from the United Kingdom Blood Service. Their telomere length was measured using special techniques. It showed that the sample population was apparently normal and displayed telomere lengths expected for their ages. The groups of people were analysed separately and then combined.

Any SNPs that showed a strongly significant association with telomere length were investigated in a second sample population. These types of study often involve this second step, known as replication, where the results of the first are confirmed in a second separate sample of people. The researchers initially set out to replicate their first test in a further 2,020 people who participated in another study, assessing their telomere lengths using the same technique in the previous samples.

The researchers then replicated their study in another cohort of 3,256 twins, although the method of telomere measurement in this group was different to the others. A further cohort of 4,216 individuals was available for testing, meaning they had replicated the initial phase of their study in a total of 9,492 people.

Further experiments were undertaken to investigate the TERC gene, the gene closest to the DNA variant. The TERC gene is involved in maintaining the length of telomeres.

What were the basic results?

The studies identified an association between telomere length and a gene variant called rs12696304 on the chromosome 3q26. The researchers say that possessing the variant is associated with a person having a shorter average telomere length that equates to about 3.6 years of age-related telomere shortening. In other words, people with this particular variant may potentially live about 3.6 years less than those without it.

It is important to note this measure only suggests a potential effect on lifespan and many other factors will determine whether or not it actually affects lifespan.

Importantly, the researchers report that the variation in telomere length explained by this particular gene variant ranged from 0.32% to 1.0% in the different cohorts. This means that in addition to the variant identified, there are many unidentified genetic and environmental factors that affect telomere length.

There was no variation in the TERC gene associated with telomere length, but the researchers say that this does not “preclude the possibility that the association with telomere length is mediated by an effect on TERC expression”. This means that it is possible that the TERC gene may be having an effect on telomere length in a process yet to be uncovered.

How did the researchers interpret the results?

The researchers emphasise the importance of telomeres in cell function and how telomere length is related to its role. They say the findings have a “broad relevance for both normal and pathological age-associated processes”.

Conclusion

This study increases the information we have about the biology of ageing. In particular, it shows an association between a gene variation and short telomeres (which have a known association with ageing).

The study was well conducted and the results are reliable. The researchers have used recognised methods in this field of research and checked their initial findings in several different separate groups of people to confirm the validity of their early associations. Their ultimate conclusion is also based on the variants that were significant across all of the cohorts analysed.

It is important to remember that while the researchers have found clear associations for a particular gene, many other genes are likely to play a combined role in ageing. In fact, the study found that the variation in telomere length, explained by this particular gene variant, ranged from 0.32% to 1.0% in the different cohorts. This means there are many other factors affecting telomere length that have yet to be identified. These are likely to be other genetic factors, although environmental factors may also play a role.

Further studies will be needed to translate these findings into technologies that can screen people for a potential raised risk of age-related diseases or improve the lifespan of individuals. The study furthers our knowledge of biological ageing but the findings also suggest that there are many other factors yet to be discovered that affect telomere length.