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This episode of Longevity by Design discusses the research behind biological aging clocks, artificial intelligence, and organ-specific aging with Dr. Alex Zhavoronkov and Deepankar Nayak.
In this episode of Longevity by Design, our hosts, Dr. Gil Blander and Ashley Reaver, MS, RD, CSSD, are joined by Dr. Alex Zhavoronkov and Deepankar Nayak. Dr. Zhavoronkov and Deepankar have extensive knowledge of biological aging clocks—how they are developed, what they measure, how to interpret them, and much more. Through valuable and ground-breaking science, they describe how artificial intelligence and biological aging clocks together shape how to view and optimize healthspan. Tune in as Dr. Zhavoronkov and Deepankar discuss the latest science in the field.
Meet Longevity by Design’s podcast guest, Dr. Alex Zhavoronkov and Deepankar Nayak
Dr. Alex Zhavoronokov is the founder and CEO of Insilico Medicine and the founder of Deep Longevity. He holds a PhD in Physics. He is joined by engineer and CEO of Deep Longevity—Deepankar Nayak.
At Insilico Medicine, Dr. Zhavoronokov and Deepankar aim to accelerate drug discovery and development by developing new AI technology. Inspired by his work at Insilico Medicine, Dr. Zhavoronokov started a second company called Deep Longevity, specifically focusing on aging biomarkers. Deep Longevity has built several patented aging clocks that predict organ-specific biological age, for example, mind, blood, microbiome, and epigenetic age. Both Insilico Medicine and Deep Longevity leverage biotechnology in the expanding longevity industry.
Artificial intelligence and age prediction
To begin the conversation, Dr. Zhavoronkov describes the role of artificial intelligence (AI) in predicting age and healthspan. Longevity biotechnology can track minute changes during a person’s life to predict age. As an example, he explains facial recognition; “The picture of your face changes in time, and because of this, AI can predict the age of your face. You can train AI with millions of pictures annotated with age, and it will recognize human age from pictures better than humans do.”
Dr. Zhavoronkov further explains that human intelligence does not understand many data types—like gene expression, MRI/CT images, pathology images, and molecular metabolic data. However, machines can be trained to predict age from data types we cannot comprehend to derive valuable biological insights. “You can actually ask AI to help interpret why it thinks that you are older or younger. Then, you can take those biological features that you derive from AI and put them into biological context—say into groups of genes, for example.”
What are biological aging clocks used for?
Dr. Zhavoronkov speaks about the differences between popular biological aging clocks, what they measure, and the benefit of each measurement.
When his team first began building age predictors using deep learning, Dr. Zhavoronkov found that predicted biological age was 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.
Therefore, the purpose of biological aging clocks is twofold—to provide an overview of your current health status and to pinpoint what to improve to live healthier longer. "We see that if you are predicted to be older than your chronological age, usually there is some kind of problem, and we want to fix this problem. Ideally, we want you to correct your behavior or look for an intervention that would make you maximally younger—so as young as possible without substantial side effects," says Dr. Zhavoronkov. He clarifies the goal is not necessarily to decrease biological age by 20 or 30 years, as this is impossible in most circumstances. Instead, with the help of AI, the goal is to reach your optimal biological age. "AI can also show you to which extent you can revert closer to your chronological age in your current health state or even become substantially younger without damaging yourself," says Dr. Zhavoronkov.
Deepankar elaborates on the value of these clocks, giving an example of how they're used in a healthcare setting. He says that his company, Deep Longevity, advocates for the use of biological age by insurance companies, saying they are a more accurate measure of a person's health. "A 45-year-old that takes care of their health, e.g., eating well, sleeping well, and regularly exercising—might belong to a cohort of 40-year-olds and vice versa. For a 45-year-old who is not living healthfully, their bloodwork may resemble a cohort of 50-year-olds, and they should be treated as such," Deepankar explains. He says this can benefit the consumer’s insurance deal and more.
How biological clocks predict aging
Deep Longevity utilizes data from many different biological aging clocks to predict healthspan, including photo age, mind age, microbiome age, epigenetic age, etc. Dr. Zhavoronkov notes they are actively working to understand how different clocks correlate.
He notes that there is a significant correlation between clocks when comparing several methodologies for measuring methylation data. Similarly, many different blood-based aging clocks yield similar correlations because they have similar features or features that are deeply correlated. But interestingly, photo age and epigenetics may trend in different directions. "Many of those clocks just do not correlate with each other, and you need to design them and develop them so they are built for a specific application. So, now we understand that if you want to develop a clock for a specific intervention, it is better to even derive it from a clock. If you change your diet, will you see a reduction in the epigenetic clock, transcriptomic clock, blood-based clock, imaging clock, and psychological clock? The answer is no; the response is very different," explains Dr. Zhavoronkov.
Organ-specific aging
Research shows that organs age at different rates, so organ-specific aging clocks are important, as advanced aging in one organ ultimately impacts the rest of the body.
Tissues that get recycled and regenerated the most (cell renewal) tend to age faster. These organs would include the liver, lungs, and kidneys, contributing to the aging processes in other organs and systems. For example, consider your lungs; if they age faster, they'll have reduced capacity and lower oxygen transport to other tissues. The same is true for the liver—if it cannot correctly process nutrients and toxins, other organs and processes with nutrient needs are impacted.
Organ-specific aging rates vary quite a bit from person to person. "We see it in the skin, we see it in hair, and we see it in our eyes. It probably is true for many other internal organs, but currently, there are no great studies to be able to reference that look at organ-specific aging in depth, so we need to have more studies to understand this better."
Epigenetic clocks
Epigenetic aging clocks are very complicated. Dr. Blander and Dr. Zhavoronkov discuss their thoughts on epigenetic clocks. He notes that epigenetic aging clocks measure cellular maturity and differentiation more so than the organism's general state of aging (biological age). "Essentially, these clocks measure how far away cells are from the embryonic stem cell state. At the embryonic stem cell state, the genome is very methylated, and many of those methylation patterns are being lost as the cell becomes more differentiated and mature." Moreover, he explains that while these clocks are valuable because they are more predictive of mortality than a person's chronological age, the number that epigenetic clocks generate may not be actionable. Therefore, it may be too early to proceed with methylation clocks as the primary data type for intervention decisions.
Advice on living a healthier longer life
Dr. Zhavoronkov’s top tip is quite simple: be optimistic. He says optimism is one of the keys to longevity and that your social connections, having a sense of purpose, and overall life satisfaction play a considerable role in your healthspan and longevity outcomes.
