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The dark side of our genes: challenges to ageing in modern times

17 May 2018
New research in Nature Review Genetics
Genes that were helpful in our evolutionary past may now predispose us to chronic diseases, such as cancer and cardiovascular diseases, writes Associate Professor Stephen Corbett.
Boy and man

Modernity has created an environment radically different from the one we evolved in.

The transition to modernity, largely driven by the Industrial Revolution, gave us easier access to food and clean water, antibiotics, vaccines, and modern medicine.

But modern times didn’t just bring us fewer infectious diseases and longer lives: they have created an environment radically different from the one we evolved in. Genes that were helpful in our evolutionary past may now predispose us to chronic diseases, such as cardiovascular diseases and cancer in older age. 

Ageing is partly caused by the combined effect of genes that are beneficial when we are young, but which drive adverse effects in older age.
Associate Professor Stephen Corbett, Charles Perkins Centre, University of Sydney

In a new paper in Nature Review Genetics by myself and an international research team, we collate evidence for the mismatch between our evolutionary past and our modern lives. We also ask whether natural selection in current generations might ultimately reduce globally the prevalence of chronic diseases that burden hundreds of millions of people in an ageing population.

Over the past four centuries, human ecology, lifestyles and life histories have changed dramatically. This transition also altered the major causes of human death.

Today, infectious diseases prevalent in childhood have given way to chronic diseases associated with ageing. Naturally, when some causes of death decrease, others must increase in proportion.

But there is another powerful force at work in the rise and fall of human disease and modern causes of death that is the increasing differences between the historical circumstances our genes evolved in and adapted to—and the new environment we live in today.

Angelina Jolie’s decision to opt for a preventive double mastectomy instead of risking breast cancer was based on her carrying a high-risk BRCA1 variant.
Professor Virpi Lummaa, University of Turku

Ageing is partly caused by the combined effect of genes that are beneficial when we are young, but which drive adverse effects in older age. These genes can influence a variety of traits and can express themselves differently as we age, a characteristic know as pleiotropy.

The term antagonistic pleiotropy describes genes that can carry both beneficial and detrimental effects. Somewhat counter-intuitively, evolution by natural selection can lead to antagonistic pleiotropy spreading in populations: the benefits received in youth outweigh the evolutionary disadvantages that accrue in older age. For example, some variants of the gene BRCA1 are beneficial to fertility but women who carry one of its variants are more predisposed develop breast cancer by the age of 90.

“Angelina Jolie’s decision to opt for a preventive double mastectomy instead of risking breast cancer was based on her carrying a high-risk BRCA1 variant,” explains the paper’s co-author, Professor Virpi Lummaa of the University of Turku.

“This gene variant hasn’t been eliminated by natural selection in the past, precisely because it also has a great benefit for female fertility. Nowadays, the situation is much worse. Due to our much lower fertility levels and longer lifespans the early benefits of such genes no longer play out,” he says.

“It is clear that there are a number of mutations that benefit fertility and have been favoured by natural selection despite heavy costs in old age. Today, these genes likely contribute to the rise of chronic disease, such as cardiovascular diseases and cancer.

“At this point, however, it’s still uncertain if they are the main cause of that increase, or just a contributing factor,” says evolutionary biologist and co-author, Dr Jacob Moorad of the University of Edinburgh.

Teasing out evolutionary impacts in real time is difficult to pinpoint because evolutionary change often requires many generations to leave an unambiguous trace in our genome.
Associate Professor Stephen Corbett, Charles Perkins Centre, University of Sydney

Teasing out these evolutionary impacts in real time is difficult to pinpoint because evolutionary change often requires many generations to leave an unambiguous trace in our genome.

How confident are we in these conclusions? In our review, we propose there is “suggestive but not yet overwhelming” evidence that natural selection, the engine of evolution, is changing course in our modern times. For example, we note several studies in pre- and post-industrial populations point to a selection toward an extended fertility period in women.

“We have to be cautious here, though,” says co-author, Professor Stephen Stearns, of Yale University. “Changes in human physique and minds are driven by two non-exclusive processes. The environment directly impacts how our genes are expressed: for example, bad nutrition in childhood can cause stunted growth. But the environment also shapes natural selection. Natural selection can make some genes to be more – and others less – frequent in the population over time: lactose-intolerance in adults is an example of this effect.

“It’s tempting to point to natural selection when we do observe a particular change,” says Professor Stearns. “But unless there is clear evidence, it is always more likely that gene expression itself has changed, rather than genes adapting themselves to a new environment.”

Betting on natural selection may not work because our modern environment is changing rapidly. The more rational response to the increase in chronic disease is to change our social environment and our lifestyles in ways that better suit us
Dr Alexandre Courtiol, Leibniz Institute for Zoo and Wildlife Research

Future studies and methodological development will help us clarify the extent to which chronic disease and genetic expression are linked and whether natural selection begins to counteract the increased burden of chronic disease. Therefore, it’s essential that we establish large multigenerational cohort studies to establish clear evidence.

Co-author, Dr Alexandre Courtiol of the Leibniz Institute for Zoo and Wildlife Research adds: “Yes, genes are guilty but waiting for natural selection to adapt our great, great, great grandchildren to our modern environment is inefficient way to ameliorate the maladaptive and continuing effects of our genetic inheritance.

Further, betting on natural selection may not work because our modern environment is changing rapidly. The more rational response to the increase in chronic disease is to change our social environment and our lifestyles in ways that better suit us. We all know the recipe: sleep more, eat less junk, be regularly active and pollute less. True, this is difficult to implement but hopefully not impossible.”

Dr Stephen Corbett is associate professor at the University of Sydney's Charles Perkins Centre and School of Public Health, and Director, Centre for Population Health, Western Sydney Local Health District.

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