Years Vs Genetic Variation: What Matters More In Determining How One Ages?

A new study explores the roles of ageing, environment and genetic variations in determining gene expression as one gets older.

The study found that after one is older than 55 years, individual genetic makeup becomes less useful in predicting which genes are expressed more or less.

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New Delhi: For years, scientists have tried to figure out how one's genetics affect the way they age. Now, a study conducted by researchers at University of California, Berkeley, has shown that individual differences in DNA matter less as one gets older and becomes prone to diseases of ageing, such as diabetes and cancer. The researchers, who studied the relative effects of genetics, ageing and the environment on how some 20,000 human genes are expressed, found that ageing and environment are far more important than genetic variation in affecting the expression profiles of several genes as people get older. 

The level at which genes are expressed or, in other words, whether the genes are maximised or minimised in activity, determines everything from one's hormone levels and metabolism to the mobilisation of enzymes that repair the body. The study describing the findings was recently published in the journal Nature Communications. 

The new study explores how age affects gene expression

In a statement released by University of California, Berkeley, Peter Sudmant, one of the authors on the paper, said a huge amount of work has been done in human genetics to understand how genes are turned on and off by human genetic variation. He added that the new project came about by asking how genes are turned on and off by an individual's age. The first result the researchers obtained was that people's genetics actually matter less the older they get. The study authors tried to find the answer to another question: how does one's genetics influence who they are, and their phenotype such as their height, weight, or whether they will have heart disease?

Years vs genetic variation: what matters more in determining how one ages?

The study said that while one's individual genetic makeup can help predict gene expression when they are younger, genetic variation is less useful in predicting which genes are ramped up or down when they are older. The authors found that after one is older than 55 years, individual genetic makeup becomes less useful in predicting which genes are ratcheted up or down. 

Though identical twins have the same set of genes, their gene expression profiles diverge as they age. This implies that twins can age much differently from each other.

Sudmant said that almost all human common diseases are diseases of ageing, including Alzheimer's, cancers, heart disease and diabetes. He explained that all these diseases increase their prevalence with age. 

Several studies are focused on identifying genetic variants that predispose one to these diseases. The new study aims to show that as one gets older, genes matter less for gene expression, and hence, researchers should be mindful of that when trying to identify the causes of the diseases of ageing. In other words, they should not focus on finding out the correlation between genetic variation and the diseases because the illnesses are driven by age, and not by genes. 

What is Medawar's hypothesis?

Medawar's hypothesis states that genes that are turned on when people are young are more constrained by evolution because genes are critical to making sure the persons survive if they try to reproduce. The genes expressed after one reaches reproductive age are less constrained by evolution. Therefore, one would expect a lot more variation in how genes are expressed later in life. The new study is in line with Medawar's hypothesis.

Sudmant said that we are all ageing in different ways. Young individuals are closer together in terms of gene expression patterns. Meanwhile, older individuals are further apart. This is because with time, gene expression patterns become more and more erratic.

Sudmant said that the study is the first to look at both ageing and gene expression across such a wide variety of tissues and individuals. The team built a statistical model to assess the relative roles of genetics and ageing in 27 different human tissues from nearly 1,000 individuals. The researchers found that the impact of ageing varies widely among tissues.

Does the environment play a role in how one ages?

Sudmant said that across all the tissues in the body, genetics matter about the same amount, and it does not seem like it plays more of a role in one tissue or another tissue. He further said that ageing is vastly different between different tissues. Age plays a much stronger role than genetics in driving gene expression patterns in the blood, colon, arteries, oesophagus, and fat tissue. 

The researchers also found that Medawar's hypothesis does not hold true for all tissues. For instance, in five types of tissues, evolutionary important genes were expressed at higher levels in older individuals. 

Sudmant said that the study indirectly indicates the effect of one's environment on ageing. The air we breathe, the water we drink, the food we eat, and the levels of physical exercise also impact our ageing. According to the study, the environment accounts for up to a third of gene expression changes with age.