Scientists from the UK and The Netherlands have identified for the first time a variant of a gene that is linked to biological ageing in humans and suggest the discovery will help us better understand cancer and diseases of ageing.
The findings of the study by researchers based at the University of Leicester and King’s College London, UK, and also at the University of Groningen in the Netherlands, were reported online in Nature Genetics on 7 February. The Wellcome Trust and the British Heart Foundation sponsored the work.
Professor Nilesh Samani, a British Heart Foundation Professor of Cardiology at the University of Leicester’s Department of Cardiovascular Sciences co-led the project and also co-wrote the paper. The other project co-leader was Professor Tim Spector from King’s College London, who is also director of the TwinsUK study.
In a press statement Samani explained that there are two forms of aging: chronological ageing and biological ageing. Chronological ageing is simply how much time has elapsed since you were born, whereas biological age is determined by certain cellular properties that make your cells younger or older than your chronological age.
One such cellular property is the length of the telomeres on the ends of your chromosomes. Every time a cell divides, its chromosomes are copied, and to preserve the information in the chromosome there are end bits that have no important DNA information: they are like buffers that protect the internal information of the chromosome, and with each replication, bits drop off the telomeres, but as long as there is still some left, the information in the chromosome is protected and passed on to the next cell generation.
Samani explained that:
“Individuals are born with telomeres of certain length and in many cells telomeres shorten as the cells divide and age. Telomere length is therefore considered a marker of biological ageing.”
“There is accumulating evidence that the risk of age-associated diseases including heart disease and some types of cancers are more closely related to biological rather than chronological age,” he added.
For the study, Samani, Spector and colleagues conducted a genome-wide association analysis of more than 500,000 genetic variations across the whole human genome to find variants sited near a gene called TERC. Altogether the analysis involved looking at the genes of over 12,000 individuals.
Spector explained that they looked at variants near TERC because the gene was already known to play a role in maitaining telomere length.
The researchers found that those individuals carrying a particular genetic variant had shorter telomeres, ie they looked biologically older.
“Given the association of shorter telomeres with age-associated diseases, the finding raises the question whether individuals carrying the variant are at greater risk of developing such diseases,” said Samani.
Spector said the findings suggest that some people are genetically programmed to age more quickly:
“The effect was quite considerable in those with the variant, equivalent to between 3-4 years of ‘biological aging” as measured by telomere length loss.”
He also said that this could mean that people with the variant may age even faster when exposed to other risks that are also “bad” for telomeres like smoking, obesity and lack of exercise. They could “end up several years biologically older or succumbing to more age-related diseases,” he added.
“Common variants near TERC are associated with mean telomere length.”
Veryan Codd, Massimo Mangino, Pim van der Harst, Peter S Braund, Michael Kaiser, Alan J Beveridge, Suzanne Rafelt, Jasbir Moore, Chris Nelson, Nicole Soranzo, Guangju Zhai, Ana M Valdes, Hannah Blackburn, Irene Mateo Leach, Rudolf A de Boer, Wellcome Trust Case Control Consortium, Alison H Goodall, Willem Ouwehand, Dirk J van Veldhuisen, Wiek H van Gilst, Gerjan Navis, Paul R Burton, Martin D Tobin, Alistair S Hall, John R Thompson, Tim Spector & Nilesh J Samani.
DOI:10.1038/ng.532
Source: University of Leicester.
Written by: Catharine Paddock, PhD