In 2021, InsideTracker launched the podcast Longevity by Design to serve as a platform for leading longevity scientists to unpack the complexities of cutting-edge research while answering the key question how can we live a healthier, longer life? Throughout season two, Dr. Gil Blander and Ashley Reaver, MS, RD, CSSD, interviewed scientists with expertise spanning many different disciplines within longevity science. They unlocked exciting information about new research findings, ongoing studies, and actions you can take today to improve healthspan.
So what did longevity scientists have their eye on in 2022? Let’s break down the eight most talked about topics of the year.
1. The distinction between healthspan and lifespan
A significant takeaway from the scientists interviewed this season was the distinction between healthspan and lifespan.
- Lifespan: The total duration of one's life, regardless of health status
- Healthspan: The duration of a person’s life spent in good health without chronic diseases or age-related disorders
The main difference between these two terms is that extending lifespan in the absence of healthspan simply means someone will live longer in suboptimal health.
Dr. Heidi Tissenbaum’s research analyzes this difference between healthspan and lifespan using C. elegans as model organisms. C. elegans are a species of roundworm that has human-like physiological changes, making it a valuable model for aging research. "In aging research, people often use lifespan synonymously with aging, but they're not the same. Lifespan is a measurement of the aging process, but the aging process is much more than how long a person lives. So we can look at two people that are the same age, and they look very different. And on the inside, it's probably even more different," she states.
During the conversation with Dr. Matt Kaeberlein, he explains that quantifying healthspan is the next big step necessary to advance the field. “Healthspan is the period of life spent free of chronic disease and disability—a period of life spent in good health. When we talk about the effect of interventions or genetic manipulations on health, we need to be precise about what we mean. There is no agreed-upon assay or set of metrics to quantify healthspan.” One metric currently used to quantify population-level healthspan is health-adjusted life expectancy (HALE), which is often presented as a proportion of life expectancy at birth and 60 years of age. However, HALE is not easy to calculate or useful on an individual level. 
Formal metrics to define healthspan would allow researchers to investigate the actions or interventions that may lengthen or shorten a person’s healthspan.
2. Personalized nutrition
Personalized nutrition is another trending topic within the field of longevity science. Dr. Eran Segal explains that individuals respond uniquely to food and may require different foods and nutrients to meet their personal needs. But to validate the effectiveness of personalized dietary choices, Dr. Segal states that there needs to be a measurable outcome or endpoint to quantify these changes.
His research team has studied continuous glucose monitors (CGMs) in relation to personalized nutrition. "We saw a lot of surprises. Foods that you would expect to cause huge glucose spikes [sugary foods] didn't occur in some people, and vice versa. At times, foods that are considered healthy spiked some glucose levels and eventually caused participants to gain weight," says Dr. Segal.
Another scientist spearheading research in personalized nutrition is registered dietitian and founder of Qina, Dr. Mariette Abrahams. Dr. Abrahams believes that personalized nutrition serves many purposes.
“At one end of the spectrum, personalization can be disease prevention or improving your health. At the other end, it can be medical nutrition, where you already have a condition. In this case, we utilize specialized products to help you improve the condition by reducing symptoms and improving biomarkers.” Personalized nutrition is a tool that can be used by everyone—regardless of health status—and account for taste, lifestyle, culture, religion, etc. Most importantly, the changes should be relevant and actionable to the individual.
In 2022, the global personalized nutrition market was estimated to be valued at $11.3 billion, and that value is projected to increase even more over the next decade. And while tech companies will continue to innovate products and solutions, Dr. Abrahams argues that to successfully deliver personalized nutrition, public partnerships are a must. "
A handful of the guests discussed whether genetics or lifestyle factors have a more significant impact on healthspan. Here's what three scientists had to say:
- Dr. Ali Torkamani explained that genetics has a strong influence on extended longevity—say living past 70 years old. However, healthspan up until 70 is driven largely by environment or lifestyle behaviors. He also clarifies that genetics are not always deterministic—even with a genetic predisposition, healthy lifestyle choices can reduce disease risk and help control disease progression.
- Dr. Nir Barzilai’s research found that centenarians and their families have a genetic predisposition that can lead to unusually high levels of a cardioprotective blood biomarker, dramatically increasing levels of high-density lipoprotein—a beneficial type of cholesterol.
- Dr. Eric Verdin cites lifestyle factors are more influential in aging than genetics. His team conducted a groundbreaking study from the Calico Group in collaboration with Ancestory.com and found that 93% of longevity appears to be determined by lifestyle factors, with just 7% attributed to genetics.
4. Calorie restriction and intermittent fasting
Calorie restriction and intermittent fasting often get lumped together, as intermittent fasting often leads to reduced energy intake. But both are trending topics in research and practice. Many of the season's guests discussed ways in which calorie restriction and intermittent fasting may benefit health outcomes.
In Dr. Raul Mostoslavsky’s episode, he explains that caloric restriction can be protective against cancer. ''Calorie restriction—where you are decreasing the availability of carbohydrates and fat as an energy source—has many beneficial effects in the context of cancer and lifespan. A lot of the original experiments on calorie restriction relate to cancer more than aging…"
Intermittent fasting expert Dr. Krista Varady shares where the scientific literature currently stands on calorie restriction and intermittent fasting, in humans. She believes that intermittent fasting is a method to consider if your goal is to lose weight—a great option for people who prefer to watch the clock instead of tracking calories. She clarifies that in humans, there are currently no clear benefits to intermittent fasting over daily calorie restriction beyond weight loss.
During this conversation, Dr. Varady shares her perspective on a popular topic of intermittent fasting that has received attention for its potential healthspan benefits: autophagy. "We are constantly bombarding our bodies with nutrients and food, and our bodies have to work to process the nutrients. With fasting, you're giving your system a rest and allowing it to look inward on itself to find dysfunctional cell components, break them down, and recycle them," said Dr. Varady. While animal and yeast models show promising results, autophagy cannot be measured in humans just yet.
5. Emerging technology
Health technology is on the rise—here’s what three longevity scientists have their eye on:
Continuous glucose monitors (CGMs): CGMs are small wearables that send blood glucose readings to a handheld device every 5-10 minutes and will alert the individual if their glucose level is too high or too low. Although traditionally used for diabetes care, CGM technology can also be used to understand how different foods and lifestyle factors impact blood glucose levels. "When you start seeing five-minute data collected over multiple days, it's surprising what foods impact your glucose. From a health and wellness perspective, it can be very insightful for people to understand how stress, sleep, different forms of exercise, and specific foods impact their glucose—and then, of course, what this means clinically," explains Dr. Matt Johnson.
Fitness trackers: As a scientist and developer whose work is at the intersection of technology, health, and performance, Dr. Marco Altini took a deep look at how fitness tracker data have improved our understanding of heart rate variability (HRV). Specifically, he emphasized that one of the defining features of HRV is how highly correlated it is with age. In contrast to heart rate, which can remain stable throughout life, HRV changes dramatically. “If you are fairly active and regularly exercise, your resting heart rate when you are 20 versus 60 can be exactly the same. This is not true for HRV, which declines dramatically as we get older, making age the strongest predictor of HRV at the population level.”
Biological aging clocks: Dr. Alex Zhavoronokov and Deepankar Nayak are business partners at Insilico Medicine and Deep Longevity and develop age predictors using artificial intelligence. Dr. Zhavoronkov has found that predicted biological age (or how old a person is internally) is inversely associated with lifespan. Individuals whose biological age was predicted to be older than their chronological age had a shorter lifespan than those with a younger biological age.
6. Gut health and digestion
Gut health is closely intertwined with various aspects of health, including longevity. The Longevity by Design hosts had the pleasure of interviewing gut health expert Dr. Filipe Gomes Cabreiro.
According to Dr. Cabreiro, the gut is essentially an ecosystem living within us that dictates our physiology. “We carry an enormous variety of microbes that produce molecules that influence our behavior, our ability to obtain nutrients, our production of vitamins, and even our communication with the immune system. Microbe diversity trains our immune system to be more aware of other pathogens,” he states.
Moreover, gut microbiome health is highly correlated with age. Dr. Cabreiro's lab has shown very clearly that by changing the composition of different microbes to produce a desired molecule, they can very strongly influence the aging process.
A gut health concern Dr. Robert Pastore aims to address is the prevalence of celiac disease in the United States, especially since 83% of celiac patients are currently undiagnosed. "Celiac prevalence is estimated to be 1 out of 100 people, and for those with a first-degree relative with celiac, your risk can be between 10-22%," says Dr. Pastore.
Diagnosing celiac disease is an important step to optimizing healthspan because many comorbidities stem from untreated celiac disease. Celiac patients also have higher rates of age-related diseases like heart disease, diabetes, and some types of cancers. Dr. Pastore strongly advocates seeking medical attention and getting tested for celiac if you present with symptoms like cramping, bloating, or regular abdominal discomfort.
7. Animal studies
Clinical trials investigating lifespan and longevity outcomes are typically conducted in animals first. And while findings from animal studies don’t always translate to humans, they offer many relevant insights.
Dr. Matt Kaeberlein is the co-director of the Dog Aging Project. The goal of the Dog Aging Project is to understand how genes, lifestyle, and environment influence aging and then use this information to help pets and people increase their healthspan.
Dr. Kaeberlein talks about how humans can apply a specific principle learned from animal studies." If there's one thing you can fix in an aging dog or an aging person, or even an aging mouse, fixing chronic sterile inflammation is going to have a big impact systemically on the function of different tissues and organs."
And caloric restriction may reduce that inflammation in mice, according to Dr. Kaeberlein. He speculates that while a 30% decrease in caloric intake is not sustainable for most humans, practicing intermittent fasting can mimic some of these results.
Dr. Tissenbaum’s roundworm studies specifically examined how sugar intake impacts the worms’ lifespan. Results showed that the roundworms consuming higher levels of sugar lived shorter than those not consuming any sugar.
8. Markers of healthy aging
In many of the episodes this season, guests discussed markers of healthy aging. According to the researchers interviewed, here are three important measurements:
Grip strength and walking speed : Grip strength and walking speed are two of the most common ways to measure age-related muscle loss at a population level, according to Dr. Roger Fielding. "Grip strength is a great prognostic indicator of late-life disability, falls, fractures, and mortality. Additionally, normal walking speed is a very strong predictor of mortality, risk of falling, and other poor clinical outcomes," he says.
LDL cholesterol, apoprotein B, and apolipoprotein A: Many lifestyle factors contribute to more advanced plaque buildup in arteries, and Dr. Ronald Krauss's research focuses on low-density lipoprotein (LDL), apoprotein B (ApoB), and apolipoprotein A or Lp(a).
Apoprotein B (ApoB) is the major structural component of potentially plaque-forming particles. There is one molecule of ApoB for each of those particles. Dr. Krauss believes that measuring ApoB in the blood provides better insight into heart disease risk than LDL since LDL cholesterol is not necessarily reflective of all particles.
Dr. Krauss also discusses Lp(a), which carries an additional protein that renders it more susceptible to oxidation, damaging the arteries. "Having elevated levels of Lp(a) has a strong genetic influence and is associated with increased risk for heart disease. About one-third of the population has high levels of Lp(a)," he explains. Therefore, Dr. Krauss strongly advocates for including Lp(a) and ApoB in standardized testing in the population to assess the risk of heart disease and provide early disease prevention.
Top tips from these scientists
At the end of each episode, Longevity by Design hosts asks each guest for their top tip to improve their healthspan and longevity. Here are the most common tips that scientists in the field of aging recommend that listeners consider implementing:
- Prioritize both cardiovascular and strength-based exercise
- Eat a well-balanced diet, with diet diversity and adequate dietary protein being important aspects
- Sleep between six and eight hours a night
- Keep an optimistic outlook and maintain happiness and contentment throughout life
The InsideTracker team extends a warm thank you to the 22 incredible guests that made season two of Longevity by Design a success.