Bryan Johnson, a 45-year-old ultra-wealthy software entrepreneur, is on a mission to reverse ageing in every organ of his body. He’s assembled a team of over 30 doctors and health experts that obsessively read the scientific literature on ageing and longevity, use Johnson as a guinea pig for the most promising treatments, and obsessively track results in every single way they know how.
Johnson’s commitment to this program doesn’t come cheap. It costs him roughly $2 million annually, and he maintains a strict daily regimen of supplements, exercise, diet, and testing; he takes over 100 different pills, works out for an hour with approximately 25 different exercises and does HIIT 3 times a week, and only eats carefully curated vegan food measured out to exactly 1977 calories. He also uses an ab machine that simulates doing 10,000 sit-ups over the course of 30 minutes that feels like, “He’s having his guts torn out of his abdomen.”
His efforts are paying off. His biological age has fallen by at least five years and he has the heart of a 37-year-old, the skin of a 28-year-old, and the lung capacity and fitness of someone who’s 18. At 6% body fat, he’s also ripped. As of December 2022, Bryan’s rate of ageing, based upon a state-of-the-art epigenetic clock called DunedinPACE, was .69, which means that for every 365 days, Bryan only ages 252. According to Bryan’s doctors, no one pushes the envelope as much as he does.
Bryan’s regimen and health stats have been made public on his website blueprint.bryanjohnson.co In his own words, “Blueprint was born after feeling helpless to stop myself from overeating to soothe the pains of life. Despite my successes, when 7 pm rolled around, there was nothing I could do to stop myself from engaging in this self-destructive behaviour. Playfully, one day, I revoked Evening Bryan’s decision-making authority to eat food. Now, my body’s 70+ organs speak for themselves, through hundreds of measurements, communicating what they need to be optimal.”
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Johnson – and even others like LeBron James and Novak Djokovic – are living proof that we can reverse, or at the very least, slow down the rate at which we age. But why do we age, to begin with; how do we measure biological age, and what does science say about age reversal?
Age reversal – the science
Bristlecone pines live for 5000 years and were already ancient when Jesus was born. Adwaita, on the other hand, was an Aldabra giant tortoise who lived for 255 years. Several other animals also possess traits that either allow them very long lives, or at least significantly longer lives than similar species, like naked mole rats, which live much longer than other rodents.
Bristlecone pines thrive in challenging environments, and we’ve found over time that this is a characteristic that all long-lived species tend to share. The key to this phenomenon is a concept called hormesis, which involves using low doses of adversity to improve health and longevity. Long-lived organisms have multiple copies of longevity genes that get turned on by adversity and protect their bodies from ageing.
We humans also possess the same longevity genes as other species and can modify our environment to manipulate these genes and extend life. David Sinclair, a genetics professor at Harvard Medical School and co-Director of the Paul F. Glenn Center for the Biology of Aging Research, believes that ageing is not inevitable and that the first person who’s going to live to be 150 has already been born.
Ageing, according to him, might even be an easier puzzle to solve than cancer or heart disease, and even now, we can significantly improve our chances of being healthy later in life by taking certain steps at any age, and our longevity genes give us insights into what these steps might be.
Genes that make us live longer
Longevity genes can be grouped into three main categories: mTOR (mammalian Target Of Rapamycin), AMPK and sirtuins.
mTOR genes sense amino acids and are activated by eating protein. Counterintuitively, low levels of mTOR activity lead to longer lifespans, and drugs, like rapamycin, that suppress mTOR, have been shown to extend lifespans in several organisms, including mice, yeast, flies, worms and even dogs.
AMPK (AMP-activated kinase), on the other hand, is an enzyme that, unlike mTOR, we want more of. AMPK senses our energy levels and responds to low levels by activating genes that protect us from potential food shortages by switching on energy-producing pathways, like glucose uptake and fatty acid oxidation, and switching off energy-consuming pathways, like protein and lipid and lipid synthesis. Activated by eating less or fasting, AMPK can also improve insulin sensitivity, boosts mitochondria, regulates other longevity genes and down-regulate mTOR.
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Hundreds of labs are studying AMPK, but the most intriguing is probably Nir Barzilai’s lab at Albert Einstein College of Medicine in New York. Barzilai is investigating whether an AMPK-activating drug called metformin can extend life and slow ageing. Metformin is presently the frontline therapy for type 2 diabetes and studies on mice have shown that it leads to better health and longer lifespans. Data from tens of thousands of people with type 2 diabetes shows something similar: those who take metformin tend to have better overall health and longer lifespans even than those who don’t have diabetes, and taking metformin also reduces the risk of cancer, and heart disease, and frailty.
The last group of longevity genes are called sirtuins. SIR stands for silent information regulator, and sirtuins work to silence unwanted genes. Three out of seven sirtuins exist in the nucleus, where they control the unravelling of DNA and the subsequent expression of genes in a process that is cell-type specific. According to the information theory of ageing, sirtuins begin to malfunction as we age, resulting in the activation of the wrong genes, leading to cellular confusion, or a loss of cellular identity, called X differentiation.
X differentiation is the main cause of many age-related diseases, including Alzheimer’s and type-2 diabetes. Type-2 diabetes, for instance, ensues when cells that line our blood vessels begin to lose their ability to make the GLUT4 transporter, which is essential for transporting glucose into cells. This causes glucose to build up in our bloodstream where it attaches to proteins, in a process known as glycation, and causes them to lose their function.
Researchers have found that fasting, exercise, and chemical activation can all help maintain the function of sirtuins.
Measuring ageing
To treat ageing, we have to be able to measure it. In 2013, researchers published a paper showing that DNA methylation can be measured to determine biological age, which, unlike chronological age, depends upon a combination of genetic, lifestyle, and environmental factors and can provide valuable insight into our overall health and disease risk.
DNA methylation involves the addition of a methyl group (-CH3) to a DNA molecule, marking that region with a flag that can influence how much of a gene is expressed. Our cells utilise methylation as a tool to regulate access to different parts of our DNA and researchers have developed epigenetic clocks that analyse changes in DNA methylation patterns and estimate biological age with remarkable accuracy.
Other methods also exist to measure biological age, but according to Tally Health, a company co-founded by David Sinclair, DNA methylation analysis is the gold standard.
Changes in DNA methylation occur predictably and can be reversed to slow down ageing, making ageing a malleable process that, contrary to popular belief, is largely within our control. Our environment and behaviours play a crucial role in regulating longevity genes and are responsible for as many as 90% of all age-related changes to our bodies.
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So the next time you’re tempted to overeat or skip working out, you now have a reason to think twice.
