Age itself plays a bigger role than genetics in gene expression and susceptibility to specific diseases as we age.
Amid much speculation and research about how our genetics affect the way we age, a University of California, Berkeley, study now shows that individual differences in our DNA matter less as we get older and become prone to diseases of aging, such as diabetes and cancer.
“How do your genetics — what you got from your sperm donor and your egg donor and your evolutionary history — influence who you are, your phenotype, such as your height, your weight, whether or not you have heart disease?” said Peter Sudmant, UC Berkeley assistant professor of integrative biology and a member of the campus’s Center for Computational Biology.
“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.”
People age differently, including former presidents.
Ronald Reagan developed Alzheimer’s disease in his late 80s and died from complications of the disease at the age of 93. Franklin Roosevelt, shown at 62, died of a brain hemorrhage at the age of 63. Jimmy Carter, shown in 2019 at the age of 95, has suffered from cancer but is now 98 years old and still active. Our genetics, the environment and our age all play important roles in our health, but which of these is the most important? A new UC Berkeley study suggests that in many cases, age plays a more important role than genetics in determining which genes in our bodies are turned on or off, influencing our susceptibility to disease. Credit: UC Berkeley
Our individual genetic makeup can help predict gene expression when we are younger, but it is less useful in predicting which genes are ramped up or down when we’re older (in this study, older than 55 years).
Identical twins, for example, have the same set of genes, but as they age, their gene expression profiles diverge, meaning that twins can age much differently from each other.
“We’re all aging in different ways,” Sudmant said. “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 study is the first to look at both aging and gene expression across such a wide variety of tissues and individuals, Sudmant said. He and his colleagues built a statistical model to assess the relative roles of genetics and aging in 27 different human tissues from nearly 1,000 individuals and found that the impact of aging varies widely — more than twenty fold — among tissues.
“Across all the tissues in your body, genetics matters about the same amount. It doesn’t seem like it plays more of a role in one tissue or another tissue,” he said. “But aging is vastly different between different tissues. In your blood, colon, arteries, esophagus, fat tissue, age plays a much stronger role than your genetics in driving your gene expression patterns.”
These five tissues happen to be the ones that constantly turn over throughout our lifespan and also produce the most cancers. Every time these tissues replace themselves, they risk creating a genetic mutation that can lead to disease.
“I guess this tells us a little bit about the limits of evolution,” he said. “Your blood, for instance, always has to proliferate for you to live, and so these super-conserved, very important genes have to be turned on late in life.
“This is problematic because it means that those genes are going to be susceptible to getting somatic mutations and getting turned on forever in a bad, cancerous way. So, it kind of gives us a little bit of a perspective on what the limitations of living are like. It puts bounds on our ability to keep living.”
Sudmant noted that the study indirectly indicates the effect on aging of one’s environment, which is the impact of everything other than age and genetics: the air we breathe, the water we drink, the food we eat, but also our levels of physical exercise. Environment amounts to up to a third of gene expression changes with age.
(Such an important message for all of us!! Gillian Eadie, Editor.)
Original Research: Open access.
“Tissue-specific impacts of aging and genetics on gene expression patterns in humans” by Peter Sudmant et al. Nature Communications