Our DNA is less important as we age in influencing our susceptibility to age-related diseases, such as diabetes and cancer.
Researchers from the University of California, Berkeley, studied the relative effects of genetics, ageing and the environment on the expression of around 20,000 genes across 27 tissues from 948 people. They found that a person's genetics is far less important than ageing and the environment in affecting which genes are turned on or off as we age.
'There's been a huge amount of work done in human genetics to understand how genes are turned on and off by human genetic variation. Our project came about by asking, "How is that influenced by an individual's age?" And the first result we found was that your genetics actually matter less the older you get.' said Dr Peter Sudmant, who led the study published in Nature Communications.
This study is the first to look at both ageing and gene expression across such a wide variety of tissues and individuals. The researchers built a statistical model to assess the relative roles of genetics and ageing in 27 different human tissues from 948 people, categorised in two groups: under 55 years of age, and over.
They found that the impact of ageing on these tissues varies 20 times more than genetics, showing that while our DNA can help predict gene expression when we are younger, it is less important when we're older.
When analysing the gene expression of identical twins, who have the same genes, the researchers noted that their gene expression profiles were different in 42 genes, suggesting a role for the environment in modulating gene expression with age. This means that identical twins can age differently.
'We're all ageing in different ways,' Professor Sudmant added. 'While young individuals are closer together in terms of gene expression patterns, older individuals are further apart. It's like a drift through time as gene expression patterns become more and more erratic.'
This research supports Medawar's Hypothesis, proposed by Nobel-prize winner Dr Peter Medawar, which is a theory that natural selection is less of a factor for people past their reproductive years, meaning that there is much more variation in how genes are expressed later in life.
'Genes which are expressed during the first part of your lifetime are highly selected...' Giuseppe Passarino, professor of genetics at the University of Calabria in Italy, who was not involved in the study, told Medical News Today, 'Evolution is based on the fact that individuals who have better fitness have more children. Thus, their genotypes will spread in the population more than those of subjects who have [fewer] children.'
However, the researchers uncovered five tissues that did not follow this hypothesis. Blood, prostate, colon, breast, and lung tissue are driven by highly controlled, functionally important genes. These genes are being expressed at a higher rate in older people and the tissues are thus more susceptible to cancerous mutations as we age.
These findings have implications for the correlation of diseases of ageing with genetic variation in humans. Professor Sudmant concludes that such studies should perhaps focus less on genetic variants that impact gene expression when pursuing drug targets.
Sources and References
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Age vs. genetics: Which is more important for how you age?
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Tissue-specific impacts of ageing and genetics on gene expression patterns in humans
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Age impacts risk of cancer and diabetes more than genetics, study finds
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New study shows age often plays a bigger role than genetics in gene expression and susceptibility to disease.
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Age vs. DNA: Which has more influence on how humans age?
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