This story is one of many that explore recent advances in the science of longevity and aging. While previous articles in this series have focused on musculoskeletal aging, this article marks a shift toward the topic of genetics. What genes are involved in aging and longevity? How are they involved? What are the therapeutic implications?
A new study from Iceland suggests that a group of 10 to 20 disease-causing genetic variants could significantly reduce life expectancy. The findings, published in The New English Journal of Medicine, emphasize that carriers of such genes can live three to 15 years less than their non-carrier counterparts. Early screening and early discovery of these harmful genes can help minimize, and possibly prevent, loss of life expectancy.
What are “actionable” genes?
The findings are based on a set of genes called “actionable”. In short, these are genes that increase the risk of a disease for which there is a therapeutic intervention. They are considered actionable because, with appropriate medical treatment, their negative health effects can be limited or completely prevented.
The term first gained traction in 2013 after the American College of Medical Genetics and Genomics (ACMG) published guidelines on how to report secondary findings; that is, discoveries about potentially harmful variants of a gene unrelated to the main objective of the test. A way to keep control over different versions of genes, essentially.
Since then, the organization has regularly updated the list of actionable genes. And in 2021, it announced that the list would be updated once a year, to help keep up to date on newly discovered genetic variants with negative health effects. The list includes genes responsible for a wide range of health problems, including cardiovascular disease, cancer and metabolic diseases.
(Un)luck of the draw
Working with a list of 73 actionable genes released by the American College of Medical Genetics and Genomics in 2021, researchers studied complete genome sequences from 58,000 Icelanders. Whole genome sequencing is a technique that allows scientists to discover the unique fingerprint of a person’s genetic information. All DNA is made up of four simple nucleotide bases: A, T, C, and G. Whole-genome sequencing presents a snapshot of the order of these bases.
Of the 58,000 participants, 1 in 25 carried actionable genes. Focusing on their effect on longevity, the researchers found that actionable genes associated with cancer had the biggest impact on life expectancy: an average decrease of three full years. For certain cancer-predisposing genes, such as a pathogenic version of the BRCA2 gene – which is linked to breast, ovarian and prostate cancer – this number has risen to seven years. And a variant of the low-density lipoprotein receptor (LDL-R) gene reduced life expectancy by six years. This gene is closely linked to high cholesterol and heart disease.
Carriers of actionable genes were also significantly more likely to die from the disease associated with the gene. For Icelanders carrying the BRCA2 variant mentioned above, the risk of dying from breast, ovarian or pancreatic cancer was seven times higher than for the rest of the population. Those with actionable genes are also at an increased risk of developing prostate cancer and are seven times more likely to succumb to the disease than non-carriers.
The researchers also discovered 10 new, potentially actionable genes that are not currently listed in the database maintained by the American College of Medical Genetics and Genomics (ACMG). Life-shortening genes are linked to chronic kidney disease, blood clotting, bleeding disorders such as hemophilia, heart muscle disease and a rare form of diabetes called maturity-onset diabetes of young (MODY).
Approximately 4% of the Icelandic population carries actionable genes. Based on large genomic studies, a similar percentage of the population in the United Kingdom and the United States carry actionable genes. As it became clear in this study, such genes absolutely he can to be shortening of life. But crucially, they don’t need to be: Population-wide genetic screening can help identify individuals predisposed to cancer, heart disease, kidney disease, and so on. Armed with this knowledge, patients and healthcare providers can design disease prevention and treatment programs tailored to each individual. From heart disease to cancer, early detection and intervention are crucial to improving health outcomes.
We have the tools for large-scale genetic sequencing and, as this study and others like it show, the need for it, what we lack is political will and policies. Initiatives like the All of us research program, founded in the United States in 2015 during Barack Obama’s term as president, are a step in the right direction. Yet such programs are currently the exception when they should be the norm. For lack of a better alternative, people often turn to home testing kits for answers; Unfortunately, these are extremely inaccurate. Genetic sequencing needs to become a routine part of early-life medical screenings to help inform patients and design effective, individualized health programs.
Until then, go out and bother your doctor for a genetic test, it could give you three more years of life, or six.
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