🍄 The Clock Strikes Young

Estimated at $25 trillion in 2021, the global longevity economy is aging steadily to be worth $35 trillion by 2026. It accounts for 20% of the global GDP. Welcome to the tick-tock boom.

Mar 10, 2023

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🍄 AudioDose: this is Alice on Sonic Mushrooms, joyfully reverse destiny here.

Hello, we’re Alice and we are always in a state of wander. For whom does the bell toll? Let Steve Horvath chime in here, Principal Investigator at the Altos Labs San Diego Institute of Science and inventor of the “Horvath” clock. He can let you know your “GrimAge,” or when your clock will stop. ‘We named it after the grim reaper because it's our very best epigenetic predictor of how long you live, how many years are left in certain ways,’ Horvath tells ALICE. The clock is in a DNA molecule and just a tiny drop of blood can predict your life span as well as your health span: the time you have left to live disease-free. ‘Artists often symbolize mortality by an hourglass, the passage of sand trickling through a small valve. Our twenty-first-century view is that the DNA molecule is the hourglass. People suspected that the DNA is the central molecule of aging, but conclusive evidence was lacking until now.’

The End of Erode?

While Horvath seems to put a horror into horology, there’s bloom with that doom. Our genes, and how well they interact with our environments and lifestyles, can change our clocks for the better. Now that scientists have identified a “longevity gene” among centenarians, we are all set up to start hacking immortality. One day a specific protein in the gene that reverses cardiovascular aging may dramatically increase anyone’s chance of becoming a centenarian. It’s just a matter of time.

But why stop at one hundred? Researchers at the University of California, Berkeley, have captured the most detailed images to date of telomerase, the enzyme that lengthens the ends of chromosomes and plays a critical role in aging. Every time a cell divides, the chromosomes are copied, but they aren’t copied all the way to the end. Consequently, telomeres gradually get shorter. In fact, we lose around fifty to two hundred base pairs each time the cell divides, creating a sort of cellular countdown clock. These images provide long-sought insight into how telomerase works and will help guide the design of drugs that target the enzyme to rewind time. So pack up the grim reaper and return to sender.

You Are Not the Age You Think You Are

Did you know you have two different ages? One is your chronological age, or the number of years since you were born. The other is biological age, which represents how quickly the cells, tissues and organ systems in your body are deteriorating. Your biological age is now considered the true measure of age and is influenced by your genes, lifestyle, behavior, the environment and other factors—identifying even more “ages” we can measure. There’s no one formula for determining your biological age, but scientists are working on it. We do know there’s a huge range. That’s why some eighty-year-olds have impressive yoga skills and are as active and productive as they were at forty, and other eighty-year-olds have slowed down or succumbed to serious diseases like diabetes, cancer and dementia. But recent studies suggest that one key variable may be our perceptions.

I Believe in Yesterday

It’s true; the first step toward immortality is to start thinking you are younger than the number of candles on your cake. Your “subjective age”—how young or old individuals experience themselves to be—has been implicated in a range of health outcomes. Yannick Stephan at the University of Montpellier, in France, and his team published a study on the relationship between subjective age and mortality. It turns out that the group who felt older than their age had an 18 to 25 percent greater risk of death over the study periods, and an even greater chance of getting age-related diseases. It’s interesting that data from three longitudinal studies, tracking more than seventeen thousand middle-aged and elderly participants, showed that most people said they felt about 15 percent younger than their actual chronological age.

There’s a longevity gene, do you have it?

It’s not all soul-selling with Disney and Dorian Gray. To reduce our biological age, start with the source: genes. The “longevity gene” is characterized by a specific protein, BPIFB4. An Italian research group introduced this protein into DNA to reverse cardiovascular aging. The study was conducted on mice with fatty plaque deposits on their arterial walls due to a high-fat diet; once given the longevity gene, they were renewed with more youthful vitality. The researchers also experimented on human blood vessels in a laboratory setting, placing the BPIFB4 protein directly into blood vessels and attained the same rejuvenating results. They also found a correlation between healthy blood vessels and higher levels of the protein in the blood. So - who knows? - you may already have the longevity gene.

Gene therapy is changing the conventional wisdom of “you’re born with it.” While we often think of our genes as fixed, they are actually mutable. In the past, scientists believed that information was passed from parent to child during development, in the womb, setting the stage for many health-related issues. But it turns out that isn’t the whole story. Today, genetics is thought to explain less than 25 percent of the body’s main disorders, with the majority caused by environmental, non-genetic factors. A new field of genetic research called epigenetics explores how our environment can influence our genes’ expression, opening the door to a new set of healthspan and lifespan disrupters (and extenders).

The Tick-Tock Generation

Horvath’s “GrimAge” clock comes from a longish line of epigenetic clocks. The original “Horvath Clock” (2013) is based on 353 epigenetic markers on the DNA and acts like a biological age calculator. He used eight thousand data sets of human DNA. The process underpinning all the clocks is called DNA methylation (DNAm), which can modify the function of your genes and affect the way your genes express themselves. Think of it like tiny on-off switches in your body. It’s a simple biochemical process: the addition of a single carbon and three hydrogen atoms (called a methyl group) to another molecule.

‘As a biostatistician, I was blown away by the strong effects of age on methylation,’ Horvath tells ALICE. ‘And I, in essence, dropped everything else. I said to myself; these epigenetic modifications are the future of aging research. I need to build biomarkers based on DNA methylation.’ Biomarkers are indexes in the body that scientists agree quantify aging and tell us how far away disease is. By analyzing the chemical tags that are added to or removed from DNA, epigenetic clocks can be used to address a host of questions in developmental biology, cancer, and aging research.

So many clocks, so little time

⏰ The “Horvath” / “Pan-Tissue” clock was the first multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. “I had a very hard time publishing it because the results were so incredible that nobody believed them. But in the end, once the paper came out and the software was available, everybody could easily verify the claims.”

⏰ “Skin & Blood” clock was next. It measures the epigenetic age of skin tissue and assorted skin cells, like keratinocytes. It applies to the dermis, epidermis, and fibroblast and can be measured by a punch biopsy from the skin or cultured cells in a dish. “My hope is, of course, that this clock could help us identify interventions that slow aging in the skin," explains Horvath. A study has also shown that the drug rapamycin— originally used to prevent organ rejection and now associated with extending lifespan by bolstering the immune system—can also slow epigenetic aging in skin cells.

⏰ The “PhenoAge” clock, (2018) uses algorithms trained to find methylation signals associated not only with chronological age, but also with a panel of aging-related phenotypic indicators, such as blood glucose and markers of liver and kidney function. Along with the GrimAge, it’s known as a “second-generation” clock, predicting age-related health outcomes better than earlier clocks can.

Leading Indicators

Longevity-focused personalized medicine certainly lurches forwards. Here’s a round up of some reverse gear.

🧠 What’s the DNAge?
Based on Dr. Steve Horvath’s Epigenetic Aging Clock, myDNAge® claims to precisely determine biological age using just a small amount of blood or urine. Next Generation Sequencing technology is used to scan over 2,000 biomarkers in the human genome that are subject to epigenetic changes, in order to accurately determine your biological age.

🧠 Reveal your TruAge
Find out how fast you are aging with TruDiagnostic, a health data company delivering more than just your biological age. Through epigenetic testing and research, they also provide a full suite of aging-related metrics including telomere length measurements, intrinsic and extrinsic age calculations, immune cell subset deconvolution and the current pace of aging. Your TruAge reports can give context to what may have influenced your various aging scores and suggest helpful health and lifestyle changes.

🧠 Your Life Line?
AgeRate is an at-home blood test and mobile app offering personalized health coaching. Created by a network of doctors, engineers and data scientists, AgeRate is currently investing in new testing methods that expand beyond epigenetics, to include proteomics and mitochondrial health.

🧠 Reelin' in the Years
Index, by Elysium Health, is an at-home test that tracks how fast you’ve been aging using the latest generation technology in the science of epigenetics—how your behaviors and environment can cause changes that affect the way your genes work. With Index you'll receive:
•Biological Age, a measure of the average age at which your body is expected to function
•Cumulative Rate of Aging, the pace at which your body has aged for every year you’ve been alive
•Science-backed lifestyle recommendations you can use to adopt healthier habits

Books we love

📘 “Aging is a disease, and that disease is treatable," writes Dr. David Sinclair, Harvard Medical School scientist, in his New York Times Bestselling book "Lifespan: Why We Age—and Why We Don't Have To." (Atria Books 2019)

📘 "Have you wondered why some sixty-year-olds look and feel like forty-year-olds and why some forty-year-olds look and feel like sixty-year-olds?" co-author Dr. Elizabeth Blackburn, "The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer." (Grand Central Publishing, 2017)

📘 "Will 100 be the new 40?" With the new advances in medicine and therapies that prolong life expectancy, humans are close to cheating death—or at least delaying it! ALICE explores both the science and cultural impulse behind hacking for life extension, and ways we can make aging even more manageable in our book "Hacking Immortality: New Realities in the Quest to Live Forever" (Tiller Press, 2021)

What else we are wandering

🔍 REM-back the years
There's another metric for determining your mortality, and it has to do with your sleep age. Stanford Medicine researchers have identified a projected age that correlates to one's health based on their quality of sleep. They assign one's sleep age using machine learning, and variations in sleep most closely linked to mortality.

🎧 Immortal consciousness
Could the information in your consciousness be part of a bigger field? Johnjoe McFadden, scientist, academic and Professor of Molecular Genetics at the University of Surrey, in the United Kingdom, and author of “Quantum Evolution," takes ALICE on a journey through consciousness; from early understandings, into today's work, and speculating where tomorrow's research may lead us.

🔍 Time jump
Scientists have developed a method to time jump human skin cells by three decades – longer than previous reprogramming methods, rewinding the aging clock in human skin cells by 30 years without the cells losing their function.

🔍 Aging Faster in Space to Age Better on Earth

🔍 Astronauts well-being and possibly anti-aging improved during long-duration spaceflight

Craving more?

📘 Alice in Futureland books
🎧 Alice in Futureland Podcasts
🎧 Deep Longevity with Alex Zhavoronkov, AI + aging expert
🎧 Hacking Immortality with Zoltan Istvan, Transhumanist
🎧 Rejuvenation and Longevity with Mickra Hamilton, Human Performance Subject Matter Expert