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Your genetics can uncover many things about you. They can influence how you look and behave, to name a few. But your genes are not deterministic; they don't tell your entire story.
In this episode of Longevity by Design, our hosts, Dr. Gil Blander and Ashley Reaver, MS, RD, CSSD, are joined by Dr. Ali Torkamani, Director of Genome Informatics at the Scripps Research Translational Institute. Tune in as Dr. Ali Torkamani discusses how genetics impact lifespan and healthspan, why genetics aren't deterministic, and how lifestyle factors promote a healthier, longer life.
Meet Longevity by Design’s podcast guest, Dr. Ali Torkamani
Dr. Ali Torkamani is a professor and the Director of Genome Informatics at the Scripps Research Translational Institute. By analyzing genetic and genomic data of many types in a systems biology framework, Dr. Torkamani hopes to advance scientific understanding of the genetic mechanisms of human diseases.
His primary focus areas include human genome interpretation and genetic dissection of novel rare diseases, predictive genomic signatures of response to therapy – especially cancer therapy, and novel sequencing-based assays as biomarkers of disease.
What is a genotype-first approach?
To begin, Dr. Torkamani explains the current way in which we use genetic information in medicine. "It's very reactive," he says, "People present with a rare disease, and then they go through genome sequencing to clarify what the disease is or the disease's genetic cause." As Dr. Torkamani puts it, the issue with current practice is that we are utilizing the genome too late.
Dr. Torkamani contrasts this with his proactive, genome-first approach. "The genotype-first approach flips this on its head. Why don't we sequence the genome when people are ostensibly healthy and make predictions about their genetic risks. Then, we can look at assortments of common genetic variants that put them at risk for disease and use that to project where their health might end in the future. With this approach, we can intervene earlier rather than reacting once the disease actually presents itself."
A sizable portion of the variability in chronic disease patients relates to or can be explained by genetics. While it is well established that lifestyle interventions can be used as a preventative measure against many common diseases, the genome-first approach takes disease prevention a step further.
Genotype vs. environment—which is more important?
The debate around the contribution of one's genetics or one's environment to healthspan often arises. When asked whether genetics or one's environment has a more significant impact on healthspan, Dr. Torkamani explains a combination of factors at play. "It is currently thought that there is a decent amount of genetics driving extended longevity—say living past 70 years old. Healthspan up until 70, however, is largely driven by environment or severe genetic diseases."
Dr. Torkamani uses cholesterol and blood glucose levels to explain further the difficulty in predicting healthspan. For example, HbA1c and glucose levels are modifiable by lifestyle. Dr. Torkamani describes that high-intensity exercise is rather successful at achieving and maintaining the optimal levels of these blood sugar markers.
On the other hand, cholesterol levels can result from both genetic and lifestyle factors. "Cholesterol tends to be highly genetic, but you can modify it," Dr. Torkamani explains. "In the presence of strong genetic predisposition—say a rare genetic variant that results in extremely high LDL levels—lifestyle intervention will probably not work. That tends to be pretty rare, however. That being said, genetics can drive high cholesterol levels for the average person, but it is possible to modify them with a healthy lifestyle." Both genetics and lifestyle are essential for determining disease risk and achieving longevity.
Heritability is not a fixed concept
A combination of factors causes most diseases—genetics and lifestyle being the most critical. Dr. Ali Torkamani clarifies that genetics are not always deterministic, despite people's beliefs. "When you look at the heritability of a particular disease, it's not a fixed concept. It changes over time, depending upon the environment. Take smoking, for example. Genetics don't have much to do with developing lung cancer for heavy smokers. However, in the absence of smoking, genetics tend to have a larger contribution to lung cancer."
Even with a genetic predisposition present, lifestyle choices can reduce disease risk and help control disease progression.
It can be challenging to separate genetics from lifestyle and environment because the two are intimately related in the context of healthspan. However, it's essential to view genetics as a component of your health, rather than deterministic. Often there are factors within one's control for a healthier, longer life.
Key takeaways from the Wellderly Study
Dr. Torkamani discusses a study he conducted on the wellderly—defined as people over 80 who have no chronic diseases. He wanted to determine the genetic factors that allow them to reach an advanced age and maintain their health. In the episode, he explains that they analyzed longevity genes and genes that increase the risk for chronic diseases. "Overall, the wellderly had a low genetic risk for Alzheimer's and lower risk for coronary heart disease." Dr. Torkamani says. "We saw this signal of healthier lifestyle overall and lower genetic risk for some of the major causes of death."
Interestingly, the wellderly population revealed another critical component. "When we took an unbiased look at the genome to see what other genetic variants are associated with this healthy aging phenotype, we found signals relating to cognition in general." Dr. Torkamani describes. "So not just Alzheimer's, but also depression, schizophrenia and other aspects of cognition. For me, this highlighted the brain-body link. Being cognitively intact and exercising the brain is an additional important factor for extended healthspan."
Advice on living a healthier longer life
When asked about one decision he makes every day to improve his health, he responds, "I really love weight lifting and strength training. I deplete the glucose stores in my muscles; then, I fill them back up with interesting snacks. That's the way I think about it."
