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In this episode of Longevity By Design, Dr. Gil Blander interviews Dr. Bartek Nogal about genetic predispositions to conditions of aging. This episode goes deep into explaining how to improve your healthspan using DNA insights. Dr. Blander and Dr. Nogal talk about bone mineral density, epigenetic age acceleration, cognitive decline, risk of elevated ApoB, grip strength, and more. Knowing your genetic predispositions to certain traits can help you fine tune your wellness plan, and Dr. Nogal and Dr. Blander explain how to do so in this episode.
Episode highlights
- Introduction: (0:00–3:40)
- What led Dr. Nogal to become a scientist (3:40–5:32)
- Moving from academia to InsideTracker (5:32–7:28)
- What is DNA? (7:28–9:12)
- How similar is DNA across animal species? (9:12–10:05)
- Single Nucleotide Polymorphisms (SNPs) (10:05–14:10)
- How polygenic scores are calculated (14:10–17:25)
- Defining heritability (17:25–22:53)
- ApoB is highly heritable (22:53–24:24)
- Why you should measure blood and DNA together (24:24–31:50)
- Science behind the new polygenic scores added to InsideTracker (31:50–38:20)
- How many SNPs are in the ApoB score? (38:20–41:20)
- Visceral fat (41:20–45:07)
- Age related muscle weakness (45:07–49:10)
- Bone mineral density (49:10–51:45)
- Chronotype—genetic predisposition to morningness (51:45–55:37)
- Lifespan DNA score (55:37–60:10)
- Epigenetic age acceleration (60:10–1:06:40)
- Cognitive aging (1:06:40–1:08:20)
- Age at menopause (1:08:20–1:10:40)
- Top tip for healthspan: (1:10:40–end)
About Dr. Bartek Nogal
Dr. Nogal holds a Bachelor's and Master's degrees in Biological Engineering from Cornell University. Following the completion of his Master's degree, Dr. Nogal worked in the biotech industry for nine years, contributing as a process development engineer. He pursued a PhD in the Structural and Computational Biology program at Scripps Research.
During his doctoral studies, Dr. Nogal employed a biophysical approach utilizing cryo-electron microscopy to understand the mysteries of neutralizing antibody responses to HIV vaccine immunogens. His research resulted in numerous peer-reviewed publications, including contributions to the journal Cell. Furthermore, his doctoral thesis work received recognition, and made the cover of the March issue of Cell Reports.
What is DNA?
Deoxyribonucleic acid, or DNA, is a biological polymer that carries the genetic instructions for an organism's development and function. DNA is central to the process of encoding genetic information from DNA into RNA, which ultimately shapes an organism's physical traits and internal processes through the production of essential proteins.
Defining heritability
Heritability is a measure used in genetics to assess the extent to which genetic factors contribute to the variation in a specific trait within a population. For instance, ApoB is a highly heritable trait, with estimates saying it is 50 percent heritable. This doesn't imply that 50 percent of an individual's ApoB levels are genetically determined. Instead, it means that approximately 50 percent of the observed variation in ApoB levels among a group of individuals can be attributed to genetic factors.
Importantly, heritability is a population-level metric and does not provide information about an individual's genetic contribution to their trait. It can vary depending on the specific population and environmental conditions, illustrating how genes and environment interact to shape traits within a given population at a particular time.
Single nucleotide polymorphisms (SNPs) are a way to measure genetic variance among populations
Single nucleotide polymorphisms (SNPs) are genetic variations that occur when a single nucleotide (A, T, C, or G) in the DNA sequence differs among individuals. SNPs are the most common type of genetic variation in the human genome. SNPs are essentially point mutations that accumulate over time within a population, often as an adaptive response to environmental conditions.
Dr. Nogal shares examples of SNPs, explaining that populations may develop SNPs to enhance their ability to absorb essential nutrients from their surroundings. Such adaptations can include increased mineral absorption from soil in regions where it is deficient or adjustments to skin pigmentation in response to differing sunlight exposure levels. These genetic changes, which occur over numerous generations, enable populations to better adapt to their specific environments.
Using SNPs to create polygenic scores for healthspan traits
Polygenic scores are a cutting-edge approach to understanding genetic predispositions to complex health traits. Advancements in genotyping technology have made it cost-effective to sequence an individual's genome, enabling comprehensive assessment of polygenic scores for various health traits. These scores are computed by surveying single nucleotide polymorphisms (SNPs) across the entire genome, and identifying statistically significant associations with a specific trait.
For example, consider LDL levels—a polygenic score for LDL incorporates multiple relevant SNPs, and the presence of these SNPs enhances predictive accuracy.
Dr. Nogal uses the new bone mineral density score to help explain how the InsideTracker polygenic scores were created. In the case of bone mineral density, approximately 900 locations within the DNA have been found to associate with variations in bone mineral density through genome-wide association studies. Each SNP's effect size is determined, reflecting its contribution to the trait of interest, such as bone density. Combining these effect sizes in a weighted sum yields a single value that situates an individual on the spectrum of risk or predisposition for that trait within the population.
InsideTracker's new genetic scores
As the principal scientist of InsideTracker’s genomics team, Dr. Nogal is excited to discuss the 10 new DNA healthspan scores with Dr. Blander. He explains that knowing your predisposition to certain traits helps you make more informed decisions to optimize your wellness.
Dr. Nogal says “the way we think about these genetic insights is basically a roadmap in your healthspan journey. These new DNA scores, your blood biomarker data, physio marker data from fitness wearables, and anything else you can track—they are all roads in your health journey that help lead you down the path to a better healthspan.”
Let's dive in.
The ApoB genetic score
Apolipoprotein B, or ApoB, is a protein that transports cholesterol and other fats in the bloodstream. ApoB serves as a key marker for assessing cardiovascular health.
ApoB is highly heritable, meaning a significant portion of an individual's ApoB levels are influenced by their genetic makeup. The InsideTracker ApoB genetic score includes almost 17,000 genetic variants, encompassing thousands distinct DNA locations associated with an individual's risk of having high or low ApoB levels. This score provides a wealth of information for predicting an individual's ApoB profile based solely on their genetic data.
ApoB explains 14% of the genetic variance among InsideTracker users
In the case of InsideTracker's user population, the combination of DNA and blood data offers a unique opportunity to explore ApoB heritability. Through linear regression analyses, it has been observed that the polygenic score for ApoB can explain approximately 14 percent of the variance in ApoB levels among InsideTracker users.
This variance is particularly meaningful when considering the practical implications. For instance, individuals in the bottom 10 percent of the polygenic score distribution tend to have an average ApoB level of around 77 mg per deciliter. Those in the top 10 percent—indicating higher genetic risk—exhibit ApoB levels closer to 110 mg per deciliter. This insight highlights the substantial impact of ApoB heritability on individuals' health outcomes within the InsideTracker user population.
Interpreting ApoB blood data and DNA scores together
So how should we interpret our blood biomarker data and DNA score for ApoB? Which one matters more? Dr. Nogal provides guidance on next steps.
Dr. Nogal says a high ApoB genetic score offers insights into both lifestyle and biology. “If your genetic risk for ApoB is high but your ApoB level is low, your lifestyle choices are likely countering your genetic predisposition,” he explains. If both genetic risk and ApoB level align, you're living up to your genetic potential. However, it is important to know that a high genetic risk for elevated ApoB may imply a higher risk of future cardiovascular events, even if you manage to improve your ApoB level through lifestyle changes. He adds that the scientific literature points to serum lipid polygenic scores encompassing layers of information that span beyond just predicting the biomarker level. He explains that people with higher genetic risk may have to lower their serum lipid levels more compared to those in average of low risk categories in order to prevent future cardiovascular events. This underscores the importance of discussing potential cardiovascular health concerns with a healthcare professional beyond biomarker management.
Visceral fat
Visceral fat is unhealthy fat surrounding internal organs. Visceral fat is an independent risk factor for metabolic disease. Most people do not know the amount of visceral fat they have, as routine check-ups do not measure it directly. Assessing your genetic predisposition to increased visceral fat can help inform lifestyle choices earlier in life to combat visceral fat accumulation.
Visceral fat is determined in part by genetics. The genetic risk score for visceral fat contains up to 190 genetic markers that can affect one’s risk of having increased visceral fat content. Dr. Nogal points out that it is possible to have increased visceral fat while having a lean figure—marking the importance of knowing your genetic risk.
Age related muscle weakness
Muscle mass and strength naturally decline throughout the lifespan. Individuals in their 70s typically have 20% less muscle mass than individuals in their 20s. Weaker muscles have a harder time supporting everyday activities, exercise, and balance. This makes muscle weakness a strong indicator of poor health and aging.
Muscle weakness results from lifestyle factors, nutrition, exercise, and genetics. This genetic risk score looks at 14 genetic markers that affect age-related muscle weakness.
Dr. Nogal explains that knowing your risk for muscle weakness helps inform which style of exercise training is best for you. While muscle weakness may not present a risk to health until after age 65, engaging in more resistance training before the age of 65 can help prevent muscle weakness, even for those who have an elevated risk.
Bone mineral density (BMD)
Bone mineral density (BMD) measures the mineral content in bones. Higher BMD indicates stronger bones. Osteoporosis, which is characterized by low BMD, increases the risk of falls and fractures. Without proper lifestyle interventions, BMD declines as we age.
Genetics play a substantial role in bone mineral density. This genetic potential score examines 991 genetic markers that influence the likelihood of having higher BMD.
Physical activity, especially resistance exercises, can help increase bone mineral density. Dr. Nogal shares the importance of this polygenic score, saying if someone knows they have an increased risk for low BMD in their 30s or 40s, this information can motivate them to engage in regular resistance training to combat their genetic risk.
Cognitive aging
Cognitive aging, commonly referred to as “cognitive decline,” is the age-related decline in cognitive abilities like memory, executive function, language, attention and processing speed, visuospatial ability, and more.
Dr. Nogal explains that genetics play a contributory role in the rate of cognitive aging. In fact, studies suggest that different genes may be involved in the decline of multiple cognitive domains at various stages of the aging process. Studies continue to uncover genetic variants that influence the rate of cognitive decline.
The genetic risk score for cognitive decline includes up to 1,220 genetic markers that can affect one’s risk of experiencing accelerated cognitive decline before the age of 70.
For those that score higher, Dr. Nogal recommends interventions like exercise, healthy diet, plenty of social engagement, and cognitively demanding tasks like puzzles.
For more science-backed strategies to delay cognitive aging, check out this article.
How to use InsideTracker’s 3 measures of biological age to promote healthy aging
InsideTracker now has three different measures of biological age—InnerAge, the epigenetic age acceleration DNA score, and the lifespan DNA score. Dr. Nogal explains how to interpret these three scores independently and in tandem.
InnerAge is measured using current blood biomarker data. InnerAge estimates your biological age based on an algorithm that compares each of your key biomarkers to your peers.
The lifespan score and epigenetic age acceleration score are both DNA markers. Studies have shown that genetic variants could differentiate between centenarians (those who reach 100+ years old) and typical older adults. InsideTracker’s lifespan score is composed of 324 genetic markers and measures one’s potential for a lifespan that is up to five years longer.
Epigenetic age acceleration (EAA) refers to the difference between an individual's estimated epigenetic age (their biological age) and their chronological age, the number of years they’ve been alive. Various algorithms, or “clocks” estimate the rate of aging, and epigenetic age is thought to capture multiple aspects of the process. InsideTracker’s genetic risk score looks at up to 24 genetic markers and is a measure of one’s predisposition to have accelerated aging.
Aging is a multidimensional process, and no single measure can assess how all of our body systems are declining over time. The three aging metrics give you different information about your lifespan and healthspan potential, interpreting them in tandem provides comprehensive information about your biological age. Dr. Nogal explains the lifespan score is your polygenic background for a longer life. The epigenetic age acceleration score is your predisposition to a specific aspect of biological aging that's highly modifiable. Meaning, if you compare the lifespan score to the epigenetic age score, the latter is a lot more modifiable by a healthy lifestyle. Then when you look at InnerAge, which is based on blood biomarkers, that's a real time readout of your biological age, which allows you to continuously measure how well your interventions are impacting your health, and indirectly giving you insight whether you’re modifying your genetic predisposition to accelerated aging.
Top tip for healthspan
Dr. Nogal’s top tip for healthspan is to engage in vigorous physical activity.
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