Does your family come from a long line of Alzheimer’s, cancer, or heart disease? Will nothing help your ageing skin or declining libido or flagging energy? Do you feel destined for belly fat and saddle bags? This book is for you.
The scientific reality is that 90 per cent of the signs of ageing and disease are caused by lifestyle choices, not your genes. In other words, you have the capability to overcome and transform your genetic history and tendencies. Dr Sara Gottfried has created a revolutionary 7-week programme that empowers us to make the critical choices necessary to change the way we age, stay younger longer, and remain healthy and vibrant for all of our days.
Dr Sara Gottfried is the author of New York Times bestsellers The Hormone Cure and The Hormone Reset Diet. She is a Harvard- and MIT-educated physician, speaker, and author. For the past 20 years, Dr Gottfried has practised integrative and functional medicine as a board-certified gynaecologist. Her unique mission to help reverse the epidemic of overwhelmed women and their resulting health issues has been featured in a wide array of print and broadcast media outlets. She lives in the San Francisco Bay Area with her husband and two daughters.
The Hormone Reset Diet
The Hormone Cure
Dedicated to my beloved patients and community.
Thank you for teaching me the mysteries of the human body.
The laws of genetics apply even if you refuse to learn them.
– Alison Plowden
I’M NO SUPERMODEL. In fact, obesity, hair loss, anxiety, and Alzheimer’s disease run in my family – not a pretty genetic picture for middle age and later life. My mother ate sparingly while pregnant with me, as was the fashion in 1967, an era of Twiggy and miniskirts. Mum’s diet turned on my famine genes while my chromosomes were being knit in her womb, meaning that I’ve had a lifelong struggle with blood-sugar problems and rapid weight gain (a lot more on these topics later). I’ve grown up idolising actresses such as Katharine Hepburn, Sigourney Weaver, Diane Keaton, and Julia Roberts. They were slim and tall, but I was pudgy and short.
Now, when I start to wonder why it’s so freaking hard to stay mentally and physically fit at fifty, I remind myself that my genes programme me to be a two-hundred-pound anxious diabetic with thinning hair. All things considered, maybe I’m not doing so badly.
Think about Angelina Jolie, Jennifer Lopez, Julianne Moore, Gisele Bündchen, and Helen Mirren. It’s easy to believe they won the genetic lottery. Perhaps they hail from a long line of superwomen with flawless skin, flat bellies, perfectly balanced hormones, and fast metabolisms.
It’s their job to look amazing, and they are extremely motivated to look good as long as possible as they age. Their taut abdominals and gravity-defying posteriors grace billboards, Victoria’s Secret catalogues, and Sports Illustrated covers. They have proportionally similar metrics: Gisele Bündchen, the world’s highest-paid model, is five feet eleven and weighs 126 pounds, and her bust-waist-hip measurements (in inches) are 35–23–35. Angelina Jolie is five feet eight, weighs 128 pounds, and measures 36–27–36. Their paycheques and magazine gigs depend on their enviable measurements. Even in her sixties, at five feet four and with 37–27–38 measurements, Helen Mirren rocked a coral bikini on a beach in Italy, looking better than me and most of my girlfriends.
That’s great for those women, but the rest of us flounder. I don’t know about you, but sometimes I feel like I was born to wrestle with my weight, skin, energy, and sex drive. In college, my weight ballooned. In medical school, my skin broke out and my adrenals broke down because of stress. I craved sugar and carbs and rarely ate vegetables. I drank gallons of coffee, hardly slept for a decade, and bought fat jeans. Then I had two kids. Need I go on?
Maybe you’ve been told that your muffin top or memory problems aren’t your fault; they are simply programmed by your genes. It doesn’t seem fair. When I was in my forties, my battle only seemed to get harder as I navigated the challenges of crazy work hours, perimenopause, grief, breast lumps, ageing parents, tight clothes, travel, and stress. Eventually, I learned that there’s a spiritual lesson in my battle with age and that my mess is my message.
The female body is magnificent, but it doesn’t come with a lifetime warranty or an owner’s manual. You’re the result of millions of years of evolution, but many of the adaptations that helped your ancestors survive are now making you fat and wrinkly and are no longer needed. But your genetic code – the DNA sequence that is the biochemical basis of heredity in all living organisms – is only a small part of the story. Your DNA is a unique, one-of-a-kind blueprint that is specific to you. Even if you haven’t been dealt platinum genes, you can still look great and age more slowly.
The fact is that scientists have found new ways for us to take control of our genes. For example, the naughty ageing genes usually associated with fat and wrinkles can be altered with diet, exercise, and other lifestyle choices. Simply put, by turning your good genes on and your bad genes off, you can actually prevent ageing – no matter how old you are.
Gisele’s measurements are unattainable for the average American woman – who is five four and 164 pounds with a thirty-eight-inch waist – but even if you have fewer of the good genes and more of the bad genes, you can still lose weight, improve your skin, and change how your DNA controls your body and mind. You don’t even need a large staff of trainers and chefs to hold you to your exercise regimen and diet; you can appear to have lucky genes whether or not you actually have them.
The truth is that around 90 per cent of the signs of ageing and disease are caused by lifestyle (and the environment created by your lifestyle), not genes.1 The neighbourhood of your body – how you live and the world you create, internally and externally – is more important than your DNA when it comes to how you look and feel now and for the next twenty-five to fifty years. So let’s clean up your neighbourhood.
I am a physician who trained at Harvard and MIT, but I was never taught the secrets to staying young. I didn’t learn about them in medical school because many of them weren’t yet discovered. It took a confluence of factors to create a new protocol for ageing slowly. It took the Human Genome Project, which wasn’t completed until 2003. It took affordable genetic testing, testing that up until five years ago cost about ten thousand dollars and now costs about two hundred dollars. It took bigger and better computers that could handle the volume of data that genomes provide – data sets that are so large and complex that novel data-processing applications had to be invented. It took me personally testing myself and, through trial and error, finding the genetic switches that control metabolism, weight, disease, and ageing. Then it took refining my protocol for thousands of patients and women who work with me online before I learned the best, most scientifically proven ways to reprogramme genes with specific lifestyle and mind-set changes.
In the process, I discovered what helps people not just look young but also feel young, and, even more exciting, I learned how DNA plays a part in overall ageing and what we can do to alter the way our DNA is expressed. Who wouldn’t want to influence her genes for the better?
Some women have asked me how this book is different from my previous books, The Hormone Cure and The Hormone Reset Diet. The first two books focus on your hormones, but this book will show you how to overcome and transform your genetic history and tendencies, particularly when it comes to ageing. Feel destined for cellulite, saddlebags, and belly fat? Nothing seems to help your ageing skin or declining libido or flagging energy? Does your family have a long history of Alzheimer’s, cancer, or heart disease? This book is for you. Let’s expand not only your life span but also your healthspan – the period during which you are able to thrive, free from disease and in hormonal harmony. Whether you are thirty-five or sixty-five, this protocol will help you prevent signs of ageing and feel healthier and stronger than ever before.
The strategy of the Younger protocol is to interpret the warning signs of age in your body – the worsening vision, the thinner skin, the weaker lungs, the faulty memory – and turn them around. My goal is not to pick off one disease at a time (such as Alzheimer’s, diabetes, or age-related cancers) but to delay or prevent all of these conditions, since they have a similar root cause: ageing in any form. This means that by delaying one condition, you delay them all. This is the basis of functional medicine, the emerging system of medicine that engages the whole person, not just an isolated set of symptoms, and works from the inside out to address the root cause of disease and accelerated ageing.
I became interested in my genetic contract – the rules of my DNA and how they are expressed in my body – when I was thirty-nine. Something happened that I didn’t expect: my cells started to betray me.
Let me explain. I was at a decent weight with a body mass index (BMI) of 25, right on the border between normal and overweight. I never thought of myself as middle-aged, but there I was, facing down forty, the official threshold. (Middle age is defined as age forty to sixty-five.) I heard from friends and family that I needed to get to my ideal body weight before forty because my metabolism would slow down precipitously then and future weight loss would come not from my belly, but from my face.
Apparently, in the physics of ageing, volume in the face equals youthful vigour. Dermatologists even have a term for it: the triangle of youth. If you draw a line across the cheeks from ear to ear and then close the triangle by drawing a line from each ear to the chin, the widest part of the face is at the cheeks. But as you age, thanks to gravity, cheeks deflate, and fat moves south. Your body makes less collagen, and the collagen that it does make is less elastic, so your skin is not as thick and firm as before. Your bones thin, so the cheekbones shrink. Excess skin moves to the jaw, and now the widest part of your face is at the jawline, and the triangle of youth flips upside down.
Was this true? I decided to separate fact from fiction by applying my medical knowledge to my own ageing body, just as I had done previously with hormones.
During this investigative period, I learned many surprising truths about ageing. Much to my dismay, I discovered that fat loss does indeed occur in a woman’s face, as opposed to her belly, after a certain age because collagen no longer undergirds the architecture of the facial skin and bones. Even so, I also learned that modulating oestrogen levels with targeted lifestyle changes can slow down the loss of collagen. (see chapter 5) to boost production of collagen type III. Despite what you may think, not everything is inevitable when it comes to ageing. I can promise you that we do have considerable control over the process.
Let’s look at what’s actually happening in your body. By the time you reach middle age, there has been an unseen, predetermined, twenty-five-year process of cellular decline. (Don’t freak out – I will show you how to circumvent this problem, no matter how close or far you are from forty.) Cellular decline progresses insidiously, unobserved by most people, perhaps including you and your well-intentioned doctor. You may notice it as muscle tightness, an emerging paunch, lingering hangovers, or difficulty reading labels, or you may recognise it by the fact that staying in shape seems to require ten times the effort. Your endocrine glands, from your ovaries to your thyroid, start to sputter and gasp in their hormone production. Then muscle mass declines and gets replaced by fat, and suddenly you realise – like I did on a recent fitness spree – that the activity of jumping is no longer an option. You start waking up at four in the morning for no good reason. Words you’ve used for decades evade you.
Unlike a fine Bordeaux, your body does not get better with age. Before you pour yourself another glass of wine to lament the facts of middle age, permit me to share some good news with you. Due to recent scientific breakthroughs, middle age now offers you a profound opportunity to reprogramme your genes and your body. I urge you to take this seriously before decay, or what we can refer to as accelerated ageing, sets in, leading to not just minor annoyances like hair loss but also alarming diseases such as Alzheimer’s and breast cancer. In fact, the Centers for Disease Control and Prevention reported that in 2015, for the first time in several years, longevity declined, due to an uptick in heart disease, diabetes, stroke, and Alzheimer’s.2 If those diagnoses seem abstract and irrelevant to you now, consider that by the year 2030, 20 per cent of the population will be sixty-five or older (compared with 13 per cent in 2010).3 New cases of Alzheimer’s will rise by 35 per cent,4 while new cases of breast cancer are expected to rise by 50 per cent.5 You don’t want to be included in those statistics.
Using my medical education and practice as well as my own very personal struggle as a woman in a middle-aged body, I have developed a seven-week programme called the Younger protocol to change the course of your ageing body and grow your healthspan.
After forty, you begin to feel the effects of getting older. You can’t indulge in French fries, sugary cocktails, and ice cream – or if you do, you can’t get away with it. Grey hairs show up. When you’re on your feet most of the day, leg veins no longer snap shut, and an unmistakable bulge of fluid collects at your ankles. You can’t read your smartwatch without glasses (happened to me last week!). Your hormones are suddenly out of whack, and you find yourself sad, moody, tired, or chubby for unclear reasons. Your back goes out when you travel. You’re not as stress resilient, and when you get a lousy night of sleep, you don’t bounce back as easily as you once did. Why? Five key factors make ageing more pronounced after forty, leading to inflammageing – the unfortunate hybrid of increasing inflammation, stiffness, and accelerated ageing. Keep in mind it’s not your age that’s the enemy, it’s the loss of function, and these are the culprits:
The net result of these five factors is a vicious cycle of more inflammation, an overactive immune system that’s ready to attack normal tissues, and faster ageing. In the following chapters, you’ll learn how to disarm, prevent, and reverse these five factors and change the expression of genes that influence them. If you are tired of the sinking feeling that you are getting older, slower, and fatter by the day, turn the page and discover how you can unlock your genes and live longer, stronger, and better than ever.
I grew up, and old.
– Alice Munro, “Some Women”
CRUCIAL TRUTHS ARE locked in your genes. When unlocked, they will forever alter the way you think about how your body ages. I started at age thirty-nine to upgrade my lifestyle and throughout my forties found benefits I never thought possible. More energy – I’ll take it. Less stress – that was a no-brainer. Glowing, thicker skin – yes, please!
Allow me to be perfectly clear: I’m not interested in the quackery or unproven potions that are rumoured to help you stave off mortality. I’m not going to suggest you start injecting yourself with age-defying hormones. Instead, I focus on the rigorous methods of smart, unbiased researchers who are optimistic about which natural efforts can result in extended vitality as well as on the cultural insights from long-lived populations around the world. I’m especially fascinated by the practical experience of my own patients, and I’ve observed which habits are the easiest to adopt and, therefore, the most successful.
Yes, ageing is inevitable. But you can delay accelerated and unnecessary ageing so that it’s a far slower and richer journey than the steady march of decline that too many women experience. I’ve discovered the exceptions to the rules of ageing so that you can disobey them too.
Meet Heather: No Fillers Required
Heather was a forty-five-year-old teacher who came to see me because of early bone loss and ten stubborn pounds she couldn’t lose. She asked me to fix her wrinkles too, because as a single woman, she had difficulty in the online dating world competing against women in their thirties with glowing skin. Encouraged by some friends, she went to an eye doctor who no longer practised ophthalmology but instead injected fillers into ageing women’s faces and necks. She came away a bit horrified by how beat up she looked for days, not to mention by the tremendous out-of-pocket expense of five hundred to a thousand dollars per area.
“Is this what it has come to, Dr. Sara? Is there an alternative to fillers?” she asked.
I made a few small changes to Heather’s lifestyle. I asked her to eat more marine fat – from cold-water, wild-caught fish and seafood – and to floss twice per day. She drank bone broth during her hours in the classroom and used it as a base for soups. We added vitamin D and DHEA to her daily regimen. She scheduled two yoga classes per week and frequent brisk walks. She returned after eight weeks, thrilled with the results. The weight fell off. Her skin was smoother. Heather radiated confidence. She looked profoundly younger, no fillers required.
For many years, I’ve been using functional medicine with clients and on myself. It is an extremely therapeutic approach that creates a healing partnership between patient and practitioner. In my professional opinion, this has been the missing piece in modern medicine. Disease results from too much or too little of anything in life. Functional medicine looks at the interactions among genetic, environmental, and lifestyle factors that can influence long-term health and disease. Having been educated in both paradigms, my opinion is that traditional medicine is essential when you have a broken bone or pneumonia, but functional medicine may be a better approach when it comes to preventing and reversing chronic disease. We want to find out if functional medicine works better or not studied against conventional medicine. The Cleveland Clinic is now performing clinical trials comparing head-to-head the standard medical treatment versus functional medical care for asthma, inflammatory bowel disease, migraines, and type 2 diabetes – watch for results in the years to come.1
Here’s a sobering statistic I learned from Bill Gifford, science writer and author of Spring Chicken: Stay Young Forever (or Die Trying): consumers spend more on plastic surgery than the government spends on ageing research.2 I’m not judging – far from it. Even though I am Dr. Natural, sometimes I catch myself looking for a long while at the noninvasive or surgical cosmetic solutions advertised on billboards and TV. What about you?
Two of the most common plastic surgeries, eyelid surgery and facelifts, are growing in popularity.3 Why are anti-ageing procedures on the rise? What motivates people to have plastic surgery as they age?4 Scientific studies show that the people most likely to go under the knife are wealthy females with low self-esteem, low life satisfaction, low self-rated attractiveness, and few religious beliefs. These women are also heavy television watchers (and perhaps see beautiful bodies on TV that they want to emulate). The common motivations? Body-image problems and reluctance to age. However, if you think that lifting, sucking, and filling are your only options, I’d like to offer you a far safer and more palatable solution.
As a doctor, I know that many patients who seek plastic surgery in middle age may not be receiving the minimum self-care necessary to stay healthy mentally, physically, and emotionally. Patients with high self-esteem tend to care for themselves by exercising, abstaining from drugs and smoking, eating well, and drinking plenty of filtered water – all preventive activities that encourage a long, healthy life. If caring for your health has not been your focus, I’d encourage you to ask yourself why. Perhaps your focus has been on your children, partner, or work. Self-care requires contemplative inquiry and self-reflection. Without it, it’s hard to become healthy, inside and out. One thing I know for certain is that self-care is more effective than plastic surgery.
I first saw Ida Keeling on Facebook when I found a photo of her in mid-push-up, sporting a huge grin and impressive deltoid muscles. She is known for the quip “Never use age as an excuse.” I was shocked to discover that she was a hundred years old. From the photo, I learned that she is a record-holder in track for the hundred-metre dash.5 That’s a lot of hundreds. There’s a sparkle in her eyes despite the triple digits of her age. She demonstrated a couple of important truths about exercise: it’s never too late to start (she began running at age sixty-seven), and most of us don’t get the right dose (along with running, Ida bikes, skips, and goes to yoga twice per week despite struggling with arthritis).
“There are people who consider themselves ‘old’ just sitting around at home and waiting to die – that’s just stupid,” Ida says. “If I could, I would tell them to stop feeling sorry for themselves and to get active, but there’s nothing wrong with recharging yourself when you need to.
“Exercise is one of the world’s greatest medicines,” Ida explains.6 Indeed, you may not realise that the dose of this “medicine” affects your longevity. You’re probably familiar with the current recommendation of one hundred and fifty minutes per week (that’s about thirty minutes five days a week). One recent study from the National Cancer Institute and Harvard University showed that for 661,000 middle-aged people followed over fourteen years, exercising at even a low dose, meaning less than the current recommendation, reduces mortality by 20 per cent. Even better news? Bump it up to an hour to two hours per day of moderate intensity and you double the benefit.7 That means you want to stay active as you age. In chapter 7, I will show you the exercises most supported by science for keeping you supple and I’ll explain how to determine the right dose for you.
The conventional wisdom is that our genes haven’t evolved much since the Great Leap Forward approximately fifty thousand years ago, when a behavioural, genetic, and cognitive leap ended significant biological evolution of humans. Genetic adaptations since then have been relatively superficial; for instance, humans becoming able to digest grains and dairy, as opposed to mostly seeds, nuts, tubers, fish, fruit, vegetables, and animal protein.
Right now we are in the midst of an epoch that will revolutionise the way medicine is practised. We’re in the era of biological design. Before scientists sequenced the entire human genome, in 2003, people figured DNA was the blueprint for the cause of all disease. Quite the contrary – researchers learned that disease isn’t hardwired into your DNA but is much more malleable, a result of complex interactions involving your DNA, your lifestyle, and your environment. Essentially, you have the power to reconfigure the way your DNA talks to your body, a process known as gene expression.
While DNA can’t explain all your biological traits, this book addresses the key genes you can influence, the ones that affect weight, ageing, appearance, stress resilience, mental acuity, and healthspan.
As you learn the backstory of your most important genes and how they interact with your lifestyle, you’ll be able to turn on the good parts of your gene expression and turn off the bad parts. I’ll share food, sleep, exercise, stress-busting, and brain-boosting ideas so that you can discover the top cures that will slow down your ageing process. Each week of the Younger protocol is introduced in a set of practices divided by topic:
After seven weeks, the Younger protocol works on an ongoing basis to keep cells dividing happily, sustain DNA-repair mechanisms, reduce your chance of a scary diagnosis like cancer or dementia, and decrease the likelihood that you’ll need a facelift or a walker. You may want to go back through the protocol once or twice a year if your new behaviours start to slip.
Are you ready to become younger?
Throughout your life the most profound influences on your health, vitality, and function are not the doctors you have visited or the drugs, surgery, or other therapies you have undertaken. The most profound influences are the cumulative effects of the decisions you make about your diet and lifestyle on the expression of your genes.
– Jeffrey Bland, Genetic Nutritioneering
GASPING FOR AIR, I traced Justina’s footsteps in the sand, determined not to bail. We were visiting my parents at their home on the Oregon coast, and my sisters and I had gone for a run on the beach. It was a typical February day in the Northwest: about fifty degrees, blustery, and drizzling. Justina, my youngest sister, pulled away in a sprint. She loves to run fast and has the type of body that looks good in everything; I mean, she could wear a bin bag and look hot. Meanwhile, my middle sister, Anna, and I tried to keep up, both of us thinking about the delicious meal my mum was making back at the beach house. The salty air misted our skin, but we were unable to talk, and we silently resigned ourselves to watching Justina win the race.
Anna, now forty-two, and Justina, age thirty-seven, are women with whom I share roughly the same genetics, but our lifestyles and, therefore, our environmental exposures and how they affect our DNA are quite different. We’re ageing at different rates because genetics isn’t everything.
Note the following terms that we’ll be using to describe the gene/lifestyle conversation.
While the science of DNA sounds like a foreign language, keep in mind that it’s easy to turn to the genetics first to identify key lifestyle elements of staying young and fit.
I started testing my own and my husband’s DNA in 2003, when I was considering pregnancy. We were looking for genetic problems that our daughter might inherit and, luckily, came up empty-handed. In 2005, I started testing more genes in myself. Why? I wanted to find out the ideal food plan for my body, the most expedient ways to lose weight, the best supplements to take, the most effective exercise regime, and what else I had passed onto my kids. Our genes mostly control enzymes that in turn influence micronutrients, detoxification, and metabolism. Based on the results of those tests, I added B vitamins, including methylated folate, and vitamin D to my daily supplement regimen. Then I started high-intensity interval training. Hallelujah! My long-standing depression disappeared almost overnight, my weight dropped, and my energy soared. I knew I was onto something important.
A few months later, not long after giving birth to my second daughter, I headed to yoga class by myself on the weekend. My husband stayed home to bond with our girls. In class, we were about to move into the peak pose, a difficult arm balance called side crane. Attempting it usually sent me toppling to one side or another. I looked down at my postpartum belly, still bigger than I wanted it to be. I could feel my breasts filling with milk; it had been a few hours since I last breast-fed my baby. Following the teacher’s detailed instructions, I planted my hands on the mat in front of me, twisted my legs to the right, engaged my core, and took flight! Up went my legs to rest on a spot just above my right elbow.
My legs stayed put, and I was perfectly balanced. I was solid – and strong. I breathed slowly and smoothly. I couldn’t imagine what was different and, at that moment, didn’t care. I marvelled at how my body had managed to retain some vestige of core strength despite the fact that I’d recently pushed a small-basketball-size baby through my pelvis. As the instructor advised us to unwind, I reluctantly came down.
Afterward, I rushed home to tell my husband. “Babe, it was amazing – side crane! My centre of balance is shifted, as if my body changed for the better after having two kids. I could have held the pose forever.” I paused and then said, “Wow, my body is older, better, and wiser than before!”
David responded with something like “That’s great; here, feed the baby,” but I knew I couldn’t ignore this dramatic change. Even after all my decades of medical education, I never thought the body could get better with age. But now I had proof. It was just the spark I needed to consider the ways that my environment, the sum of all of my lifestyle choices, affected the way my DNA communicated within my body. Just as having a baby, trying to reclaim my body with core work, and a shift in my centre of gravity had made me successful at mastering a difficult yoga pose, perhaps my patients could partner with me to determine how to become successful at mastering the targeted lifestyle choices that would best express their DNA.
You have about twenty-four thousand genes in your body. While many genes are important for preventing or reversing the ageing of your body and mind, after years of testing my patients and creating customised protocols for them, I’ve found that we can narrow down your long list of genes to the top seven that matter most. I know it’s probably been a while since your last biology class, so let’s start with a little background. All of us possess twenty-three pairs of chromosomes, the package containing most of the DNA in your body (there’s a tiny bit of additional DNA in your mitochondria that you received from your mother only). Before a cell divides, the chromosomes in the nucleus duplicate, and then the cell splits, distributing the sets of DNA evenly between two daughter cells. This process of cell division allows for growth, repair, or replacement of cells. See the figure here for the locations of these seven genes.
Overall, the human genome is about 99.5 per cent the same from one individual to the next, but the 0.5 per cent difference accounts for characteristics such as eye colour and body shape. Each person is unique because some genes appear in different forms, called genetic variants. If a variation occurs in more than 1 per cent of the population, it’s referred to as a polymorphism. These variants can be categorised according to function and are due to small differences in the DNA code that change the gene in a positive or negative way. Variations result from evolution, sometimes as a result of mutations, which occur randomly in an individual and are considered an abnormal change in the gene. Certain factors – what you eat and drink, how much you sleep, how you cope with stress – can turn these genetic variants on or off.
When I tell you the names of the top seven genes, they’re going to sound bizarre. Most of them seem like meaningless strands of letters and, sometimes, numbers. There’s an important longevity gene that I’ll describe in a moment called forkhead/winged helix box gene, group O3 (FOXO3 for short, pronounced “fox-oh-three”). Really, that’s the best name they could come up with? It makes you want to grab the scientists by the shoulders and give them a little shake. Instead, just treat the names of the genes like licence plates – important, but tough to remember. Use the easier nick-names whenever possible.
Of course, there are other important genes besides the top seven. For example, I have a gene variant that makes me more likely to lose weight when I eat more fish than meat. It’s called PPARγ, which stands for “peroxisome proliferator-activated receptor gamma.” It controls how the body responds to certain types of fat. One study showed that women who have this gene lose weight when they consume more than 50 per cent of their fat from the omega-3s and omega-6s found in fish, shellfish, and nuts.1 So by eating more fish and nuts, I lost weight, and you can too (if you have the same gene). You’ll learn more about this gene in chapter 5.
In the top seven, I’ve included the genes that come up repeatedly and have the greatest impact on your healthspan when targeted by lifestyle changes. In other words, they have the strongest gene-environment interaction. As an example, I am fortunate to have inherited normal versions of the genes BRCA1 and BRCA2; the abnormal or variant versions may cause a higher risk of breast cancer. (Other women in my family weren’t as lucky as I was.) An example of one of my variant genes is Fatso, described below, which makes me more likely to be hungry, unsated by food, and fat compared with someone with a normal Fatso gene.
I will help you determine whether these seven genes are working for or against you. With each week of the Younger protocol, you’ll learn how to turn on and off each gene as appropriate to balance the way these seven genes are expressed, which may help thwart the ageing process.
Official name: Fat mass and obesity associated (FTO) gene
Location: Chromosome 16
Job: This gene is strongly associated with your body mass index and, consequently, your risk for obesity and diabetes. When you have the variant, it gives you sloppy control of leptin, a hormone in charge of satiety. In other words, you’re hungry all the time.
Your task: You can turn off the Fatso gene with exercise and a low-carbohydrate food plan that’s high in fibre.
Official name: Methylenetetrahydrofolate reductase (MTHFR) gene
Location: Chromosome 1
Job: The Methylation gene provides instructions for making an enzyme that plays an important role in the processing of vitamin B9 and amino acids, the building blocks of proteins. It also helps you detoxify alcohol.
Your task: Work around a defect in the Methylation gene by eating adequate folate – not too little, which may lead to depression, high blood pressure, heart disease, stroke, addiction, and cancer.
Official name: Apolipoprotein E gene
Location: Chromosome 19
Job: The APOE gene instructs cells to make a lipoprotein that combines with fat and transports cholesterol particles in the blood and brain. People with the bad variant of this gene, APOE4 (or sometimes APO-e4), don’t recycle cholesterol, leading to higher levels of low-density lipoprotein (LDL, or bad cholesterol) in the blood. Women with APOE4 have a threefold greater risk of developing Alzheimer’s disease.
Your task: When the good variant (APOE2 or APOE3) is turned on, you may lower your risk of heart attack, stroke, and Alzheimer’s disease. When you have one or two copies of the bad variant (APOE4), you will want to turn it off with the strategies in the Younger protocol, such as sticking to an anti-inflammatory diet, exercising, keeping your blood sugar stable, and getting restorative sleep.
Official names: BRCA1 (from “BReast CAncer gene one”) and BRCA2 (from BReast CAncer gene two”) genes
Locations: Chromosome 17 (BRCA1) and chromosome 13 (BRCA2)
Job: The BRCA genes belong to a class of tumour-suppressor genes that repair cell damage and breaks in DNA and that keep breast cells growing normally. When you inherit the variant, you may not be able to prevent breast tumours from forming. Overall, one in four women with breast cancer are known to have a gene variant. There are thousands of variants of these breast cancer genes, and there are probably another hundred other breast cancer genes (such as TP53, PTEN, CHEK2, ATM, and PALB2).2 Even for women with BRCA1 and BRCA2, the range in risk is broad: 20 per cent in some people, and 90 per cent in others, which means out of one hundred women with the BRCA1 or BRCA2 mutation, somewhere between twenty to ninety will develop breast cancer over their lifetimes. Without intervention, a woman with a BRCA gene mutation is seven times more likely than other women to get breast cancer (and thirty times more likely to get ovarian cancer) by age seventy.
Your task: Turn off the breast cancer genes by eating more vegetables and less inflammatory meat, drinking less alcohol (no more than one serving twice per week), and keeping your inner clock ticking at a normal pace.
Official name: Vitamin D receptor (VDR) gene
Location: Chromosome 12
Job: VDR codes for the nuclear hormone receptor for vitamin D3, which enables your cells to absorb vitamin D. When you inherit the variant, you are more likely to suffer from bone loss.
Your task: If you have a bad variant, like I do, you need to open the vitamin D receptor by keeping your vitamin D blood levels even higher than recommended by conventional doctors, with a target range of 60 to 90 ng/mL. My vitamin D receptor functions at half the level of a normal VDR, so I keep the amount of vitamin D in my blood at about double the recommended level in order to work around my bad variant. Put another way, your task may be to raise your intake of vitamin D beyond the standard recommendation of 1,000 to 2,000 IU per day.
Official name: Circadian locomotor output cycles kaput gene
Location: Chromosome 12
Job: This gene modulates circadian rhythm, or the twenty-four-hour biological sleep-wake cycle. If you have the bad variant, you will have higher blood ghrelin levels (the hormone that makes you hungry) and resistance to weight loss. Other hormones released on a circadian clock will be affected.
Your task: Protect your circadian rhythm, keeping your body on a normal sleep-wake cycle, one of the most important regulators of your hormone production. You must get the right amount of sleep to lose weight if you have the bad variant of this gene.
Official names:
Locations: Chromosome 1 (mTOR), chromosome 6 (FOXO3), and chromosome 10 (SIRT1)
Job: Your longevity genes regulate cell growth, proliferation, motility, survival, and protein synthesis. Some variants are associated with a shorter life; others with a longer life.
Your task: Switch the longevity genes to a longer healthspan, which is sometimes performed differently for each gene. For instance, sitting in a sauna for twenty minutes turns on the FOXO3 longevity gene. Intermittent fasting turns on SIRT1 and turns off the mTOR gene; when hyperactive, mTOR is associated with Alzheimer’s disease, cancer, and early mortality.
When your body is ageing fast, there are several telltale signs:
The extent of these changes are actually measurable in your blood by way of a test for telomere length. You have timekeepers in your cells called telomeres. A telomere is a collection of DNA at the end of your chromosome that acts like a knot at the end of a thread. A telomere signals to the enzymes duplicating your DNA that they’re almost at the end of the strand and it’s time to stop, just as a knot tells you to stop pulling a piece of thread with a needle. For nearly all normal cells, each time a cell divides, its telomeres get shorter. At a certain point, the cell dies because the telomeres are gone and the ends of the chromosomes are no longer protected. It’s normal to lose telomere length as you age, but only at a certain, healthy rate. Some people lose length on their telomeres faster than average.
You Don’t Have to Test Your Genes
With all this talk about your DNA, you may wonder if you need to test yourself to benefit from this book. In a word: no. As I mentioned, 99.5 per cent of human DNA is identical from one individual to the next, so maximising the way your DNA functions is very much the same for all of us when it comes to ageing. Furthermore, you have a ton of genes! In one study that looked at 2.8 million genes in 320,485 individuals, one hundred genetic variants were found to contribute to BMI, and they don’t change as you get older.3 The reason I’ve chosen the Fatso (FTO) gene is that it has the largest impact of all the hundred genetic variants – in other words, the Fatso gene holds the greatest potential for change in your body.
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If you decide to test, it is increasingly more affordable. At the time of the writing of this book, it costs about two hundred dollars to map important genes (see Resources). In the future, I predict most of us will be running around with our own genomes printed on smart cards kept in our wallets. This will allow for a more personalised approach to preventing disease and unnecessary ageing. Until that day arrives, the Younger protocol can produce anti-ageing results even without genetic testing.