Eventually these tired cells reached a stage he called senescence: They were still alive but they had all stopped dividing, permanently. This is called the Hayflick limit, the natural limit that human cells have for dividing, and the stop switch happens to be telomeres that have become critically short.
Cells don’t always have a Hayflick limit, because they have telomerase. Stem cells, if kept healthy, have enough telomerase to enable them to keep dividing throughout our life spans.
Senescent cells can leak pro-inflammatory substances that make you vulnerable to more pain, more chronic illness. Eventually, many senescent cells will undergo a preprogrammed death.
Telomeres, which can be measured in units of DNA known as base pairs, are like the aglets; they form little caps at the ends of the chromosomes and keep the genetic material from unraveling.
But when a cell’s telomeres become too short, they send out signals that put the cell’s cycle of division and replication under arrest. An arrested cell stops in its tracks. The cell can no longer renew itself. It becomes old; it becomes senescent. If it is a stem cell, it goes into permanent retirement.
Aging can be defined as the cell’s “progressive functional impairment and reduced capacity to respond appropriately to environmental stimuli and injuries.”
The UV rays from sun exposure can damage telomeres.
Skin cells, when protected from the sun, can withstand aging for a long time.
Special cells inside the follicle — melanocytes, the same kinds of cells responsible for skin color — inject the hair with pigment. Without these natural hair-dye cells, hair color is lost. Stem cells in the follicle produce the melanocytes. When these stem cells’ telomeres wear down, the cells can’t replenish themselves fast enough to keep up with hair growth, and gray hair is a result. Eventually, when all the melanocytes have died, hair becomes pure white.
People with the shortest telomeres are on average the ones who are sicker, weaker, or whose faces show the strain of coping with health problems like diabetes, cardiovascular disease, a weakened immune system, and lung diseases.
People who tend to focus their minds more on what they are currently doing have longer telomeres than people whose minds tend to wander more. Other studies find that taking a class that offers training in mindfulness or meditation is linked to improved telomere maintenance.
The telomere is so preoccupied with protecting itself that even though the cell has called out for help, the telomere won’t let the help in.
This unremitting but futile signaling can have devastating consequences. Because now that cell becomes like the rotten apple in the barrel. It starts affecting all the tissues around it. The SASP process involves chemicals like pro-inflammatory cytokines that, over time, travel through the body, leading to system-wide chronic inflammation.
Amazingly, the Texas researchers found that when people had short telomeres in their white blood cells (which serve as a window into telomere length throughout the body), their hippocampuses were smaller than those of people with longer telomeres. The hippocampus is made up of cells that need to regenerate—and if you want to have good memory function, it’s essential for your body to be able to replenish the hippocampus’s cells.
Be careful of how you think about old people. People who internalize and accept negative age stereotypes may become age stereotypes—they may develop more health challenges. This phenomenon is called stereotype embodiment.
“Age is an issue of mind over matter. If you don’t mind, it doesn’t matter.”
Telomere DNA
At the ends of chromosomes was a simple, repeated DNA sequence. The same sequence, over and over and over. I had discovered the structure of telomere DNA.
The DNA of telomeres is different. First of all, it doesn’t live inside any gene. It sits outside of all the genes, at the very edges of the chromosome that contains genes. And unlike genetic DNA, it doesn’t act like a blueprint or code. It’s more like a physical buffer; it protects the chromosome during the process of cell division.
Telomere length declines with age, on average. It declines fastest during early childhood and then has a slower average rate of decline with age.
Telomerase is the enzyme responsible for restoring the DNA lost during cell divisions. Telomerase makes and replenishes telomeres.
Telomerase can slow, prevent, or even reverse the shortening of telomeres that comes with cell division.
Too much telomerase, spurred by the actions of even normal variants of telomerase genes, can increase risks of developing several forms of cancer. And overactive telomerase fuels most cancers once they turn malignant.
Negative stress and pessimism
The more stress you are under, the shorter your telomeres and the lower your telomerase levels.
It also meant that our life experiences, and the way we respond to those events, can change the lengths of our telomeres. In other words, we can change the way that we age, at the most elemental, cellular level.
In our caregivers, several aspects of the physiological stress response, including lower vagus activity during stress, and higher stress hormones while sleeping, were linked to shorter telomeres or to less telomerase.
Whereas the threat response prepares you to shut down and tolerate the pain, the challenge response helps you muster your resources. Your heart rate increases, and more of your blood is oxygenated; these are positive effects that allow more blood to flow where it’s needed, especially to the heart and brain. (This is the opposite of what happens when you’re threatened. Then, the blood vessels constrict.) During the challenge response, your adrenal gland gives you a nice shot of cortisol to increase your energy—but then your brain quickly and firmly shuts off cortisol secretion when the stressful event is over. This is a robust, healthy kind of stress, similar to the kind you may have when you exercise. The challenge response is associated with making more accurate decisions and doing better on tasks, and is even associated with better brain aging and a reduced risk of developing dementia.
When you can’t control the difficult or stressful events in your life, you can still help protect your telomeres by shifting the way you view those events.
The brain is wired to predict things ahead of time, not just react after things have happened. The brain uses memories of past experiences to continually anticipate what will happen next, and then corrects those predictions with both the current incoming information from the outside world, and from all the signals within our body. Then our brain comes up with an emotion to match all of this.
Knowing how emotions are created is powerful. Once you know this, you can have more choice over what you experience.
When research volunteers are told to interpret their body’s arousal as something that will help them succeed, they have a greater challenge response.
When you anticipate a bad outcome before an event has even begun, you increase your dose of threat stress, and that’s the last thing you need. But rather than avoiding thinking about stressful things, it’s how we think about them that matters.
Because we have such a huge variety of different T-cells, when we become infected with a particular virus, the few T-cells that have the correct receptor for the virus must create many progeny in order to combat the infection. During this massive process of cell division, telomerase is ratcheted up to high levels. However, it simply can’t keep up with the speedy rate of telomere shortening, and eventually the telomerase response weakens to a whisper, and the telomeres in those responding T-cells keep getting shorter. So they pay for those heroic responses. When a T-cell’s telomeres grow short, the cell becomes old, and it loses the CD28 surface marker that is necessary for mounting a good immune response. The body becomes like a city that’s lost its budget for police helicopters and searchlights. The city looks normal from the outside, but lies vulnerable to criminal infestation. The antigens on bacteria, viruses, or cancerous cells are not cleared from the body. That’s a reason people with aging cells—including the elderly and the chronically stressed—are so vulnerable to sickness, and why it’s hard for them to weather diseases like the flu or pneumonia. It’s partly why HIV progresses to AIDS.
When the telomeres of aging CD8 cells wear down, the aging cells send out proinflammatory cytokines, those protein molecules that create systemic inflammation. As the telomeres continue to shorten and the CD8 cells become fully senescent, they refuse to die and they accumulate in the blood over time.
Your telomeres don’t sweat the small stuff. Toxic stress, on the other hand, is something to watch for. Toxic stress is severe stress that lasts for years. Toxic stress can dampen down telomerase and shorten telomeres. Short telomeres create sluggish immune function and make you vulnerable even to catching the common cold. Short telomeres promote inflammation (particularly in the CD8 T-cells), and the slow rise of inflammation leads to degeneration of our tissues and diseases of aging. We cannot rid ourselves of stress, but approaching stressful events with a challenge mentality can help promote protective stress resilience in body and mind.
Cynical hostility is defined by an emotional style of high anger and frequent thoughts that other people cannot be trusted.
People who score high on measures of cynical hostility often cope passively by eating, drinking, and smoking more. They tend to get more cardiovascular disease, metabolic disease, and often die at younger ages. They also have shorter telomeres. In a study of British civil servants, men who scored high on measures of cynical hostility had shorter telomeres than men whose hostility scores were low.
When our research team conducted a study on pessimism and telomere length, we found that people who scored high on a pessimism inventory had shorter telomeres. This was a small study, of about thirty-five women, but similar results have been found in other studies, including a study of over one thousand men. It also fits with a large body of evidence that pessimism is a risk factor for poor health. When pessimists develop one of the diseases of aging, like cancer or heart disease, the disease tends to progress faster. And, like cynically hostile people—and people with short telomeres generally—they tend to die earlier.
The women with the highest levels of self-reported mind wandering (which we defined as low present-oriented focus along with wanting to be somewhere else) had telomeres that were shorter by around two hundred base pairs. This was regardless of how much stress they had in their lives. That’s why it’s a good habit to notice if you are having thoughts of wanting to be somewhere else. That thought reveals an internal conflict that creates unhappiness. This type of negative mind wandering is the antithesis of a mindful state.
Splitting your attention by multitasking is a low-grade source of noxious stress, even if you are not aware of it.
Thought suppression is a royal road to chronic stress arousal and depression, both of which shorten your telomeres.
Resilient thinking is encompassed in a new generation of therapies based on acceptance and mindfulness. These therapies don’t try to alter your thoughts. Instead, they help you change your relationship to them.
Personality traits like cynical hostility and pessimism may damage your telomeres, but there’s one personality trait that appears to be good for them: conscientiousness. Conscientious people are organized, persistent, and task oriented; they work hard toward long-term goals—and their telomeres tend to be longer.
This finding is important, because conscientiousness is the personality trait that is the most consistent predictor of longevity.
People high in self-compassion react to stress with lower levels of stress hormones, and they have less anxiety and depression.
How the fourteenth Dalai Lama wakes up: “Every day, think as you wake up, today I am fortunate to be alive, I have a precious human life, I am not going to waste it.” It’s too easy to never have this thought and to miss this life-affirming perspective.
Getting to know our habits of thinking is an important step toward wellbeing. Negative styles of thinking (hostility, pessimism, thought suppression, rumination) are common but cause us unnecessary suffering. Fortunately, they can be tempered. Increasing our stress resiliency—through purpose in life, optimism, unitasking, mindfulness, and self-compassion—combats negative thinking and excessive stress reactivity. Telomeres tend to be shorter with negative thinking. But they may be stabilized or even lengthened by practicing habits that promote stress resiliency.
Telomere maintenance also shows plasticity. For example, in humans and rats it looks like telomeres likely shorten a small amount at the time of a stressful event, but in most cases they can eventually repair themselves.
Exercise
Like humans, mice who are under stress develop an excessive number of mitochondria. It appears that their mitochondria are faulty and not working efficiently. Their cells are thus working desperately to increase their energy supply, with limited success.
Major stress, depression, and anxiety are linked to shorter telomeres in a dose-response fashion. But in most cases, these personal histories can be erased,
People who exercise spend less time in the toxic state known as oxidative stress. This noxious condition begins with a free radical, a molecule that is missing an electron. A free radical is rickety, unstable, incomplete. It craves the missing electron, so it swipes one from another molecule—which is now unstable itself and needs to steal a replacement electron of its own.
The danger seems to occur when free radicals build up. And when you have more free radicals than antioxidants, you enter an imbalanced state of oxidative stress.
Just as short-term psychological stress can toughen you up and increase your ability to handle difficulty, the physical stress of moderate-intensity regular exercise ultimately improves the antioxidant–free radical balance so that your cells can stay healthier. Your cells soak up the benefits of exercise in other ways, too. When you exercise regularly, the cells in your adrenal cortex (located inside your adrenal glands) release less cortisol, the notorious stress hormone. With less cortisol, you feel calmer. With regular exercise, cells throughout your body become more sensitive to insulin, which means your blood sugar is more stable.
People who exercise regularly have lower inflammatory cytokine levels, respond more successfully to vaccinations, and enjoy a more robust immune system.
Moderate aerobic endurance exercise, performed three times a week for forty-five minutes at a time, for six months, increased telomerase activity twofold. So did high-intensity interval training (HIIT), in which short bursts of heart-pounding activity are alternated with periods of recovery. Resistance exercise had no significant effect on telomerase activity (although it had other benefits; the researchers concluded that “resistance exercise should be complementary to endurance training rather than a substitute”). And all three forms of exercise led to improvements in telomere-associated proteins (such as telomere-protecting protein TRF2) and reduced an important marker of cellular aging known as p16. They also found that regardless of exercise type, those who increased their aerobic fitness the most had greater increases in telomerase activity. This tells us it’s the underlying cardiovascular fitness that matters most.
Exercise causes a brief stress response, which triggers an even bigger restorative response. Exercise damages molecules, and damaged molecules can cause inflammation. However, early on in a bout of exercise, exercise induces autophagy, the Pac-Man-like process that eats up damaged molecules. This prevents inflammation. Later in the same exercise session, when there are too many damaged molecules, and autophagy can no longer keep them under control, the cell dies a quick death (called apoptosis), in a cleaner way that doesn’t lead to debris and inflammation. Exercise also increases the number and quality of those energy-producing mitochondria. In this way, exercise can reduce the amount of oxidative stress. After exercise, when your body is recovering, it is still cleaning up cell debris, making cells healthier and more robust than before exercise.
For telomere health, you need to get regular exercise and you need to be fit.
When endurance athletes are compared to more ordinary runners, who might run around ten miles a week, you find that both groups have nice, healthy telomeres compared to the more sedentary group—and that there appears to be no additional benefit for the ultra-long-distance endurance group in terms of telomeres.
The most important time to exercise is exactly when you might not want to—when you are feeling overwhelmed. Exercise can improve your mood for up to three hours after working out and can reduce stress reactivity.
People who exercise have longer telomeres than those who don’t. This is true even for twins. It’s the increased aerobic fitness that is most tied to good cell health. Exercise charges up the cell clean-up crew, so that cells have less junk buildup, more efficient mitochondria, and fewer free radicals. Endurance athletes, who have the best fitness and metabolic health, have long telomeres. But those telomeres are not much longer than those with moderate exercise. We don’t need to aspire to extremes. Athletes who overexercise and burn out develop many physical issues, including risk of shorter telomeres in their muscle cells. If you have a high-stress life, exercise is not just good for you. It is essential. It protects you from stress-shortened telomeres.
Sleep
When you don’t sleep well, you get less REM in the second half of the night, and that results in higher levels of cortisol and insulin, which stimulate appetite and lead to greater insulin resistance. In plain terms, this means that a bad night of sleep can throw you into a temporary prediabetic state. Studies have shown that even one night of partial sleep, or one night without enough REM sleep, can lead to elevated cortisol the next afternoon or evening, along with changes in the hormones and peptides that regulate appetite and lead to greater feelings of hunger.
Getting at least seven hours of sleep or more is associated with longer telomeres, especially if you are older.
Keeping a good sleep-wake rhythm—going to bed and waking up at regular times—may be critical to your cells’ ability to regulate telomerase.
People who used an e-reader immediately before bed released around 50 percent less melatonin than people who read from a print book.
With sufficient sleep you will feel less hungry, less emotional, and lose fewer telomere base pairs. Telomeres like at least seven hours of sleep. Many strategies can help us boost our sleep quality, some as simple (but hard) as removing electronic screens from our bedroom. Try to minimize the effects of sleep apnea, snoring, and insomnia. These problems are common later in life. And when insomnia visits, use comforting thoughts to soften the alarming ones. If you have severe insomnia, cognitive-behavioral therapy can help.
Dieting and obesity
Being overweight (and not obese) is, surprisingly, not linked strongly to shorter telomeres (nor is it strongly linked to mortality). Here’s the reason: weight is a crude stand-in measure for what really matters, which is your metabolic health.
When a mouse’s telomeres are shortened throughout its body (through a genetic mutation), its pancreas’s beta cells are not able to secrete insulin. And the stem cells in the pancreas become exhausted; they run out of telomere length and can’t replenish the damaged pancreatic beta cells that should have been doing the work of insulin production and regulation. These cells die off. Type 1 diabetes steps in and begins its malevolent work. In the more common type 2 diabetes, there is some beta cell dysfunction, and so short telomeres in the pancreas may play some role there as well.
Abdominal fat is more inflammatory than, say, thigh fat. The fat cells secrete proinflammatory substances that damage the cells of the immune system, making them senescent and shortening their telomeres.
But when you withhold junk food most of the time, giving it to them only every few days, something even more disturbing happens. The rats’ brain chemistry changes; the brain’s reward pathways start to look like the brains of people who are suffering from drug addiction. When the rats don’t get their sugary, chocolaty rat junk food, they develop withdrawal symptoms, and their brains release the stress chemical CRH (short for corticotropin-releasing hormone). The CRH makes the rats feel so bad that they are driven to seek the junk food, to get relief from their stressed state of withdrawal. When the rats finally do get the chocolaty stuff, they eat it as if they will never have the chance again. They binge.
Dieting can create a semiaddictive state, and it’s also just plain stressful. Monitoring calories causes cognitive load, meaning that it uses up the brain’s limited attention and increases how much stress you feel.
The women who answered in ways that revealed a high level of dietary restraint had shorter telomeres than carefree eaters, regardless of how much they weighed.16 It’s just not healthy to spend a lifetime thinking about eating less. It’s not good for your attention (a precious limited resource), it’s not good for your stress levels, and it’s not good for your cell aging.
Instead of dieting by restricting calories, focus on being physically active and eating nutritious foods
For now, it looks as if caloric restriction has no positive effect on human telomeres.
Telomeres tell us not to focus on weight. Instead, use your level of belly protrusion and insulin sensitivity as an index of health. (Your doctor can measure your insulin sensitivity by testing your fasting insulin and glucose.) Obsessing about calories is stressful and possibly bad for your telomeres. Eating and drinking low-sugar, low-glycemic-index food and beverages will boost your inner metabolic health, which is what really matters (more than weight).
Nutrition
One of the best ways for you to protect yourself against inflammation is to stop feeding it. The glucose absorbed from French fries or from refined carbohydrates (white bread, white rice, pasta), and from sugary candies, sodas, juices, and most baked goods, hits your bloodstream fast and hard. That uptick of blood glucose also causes an increase in cytokines, which are inflammatory messengers.
For a start, we can simply eat the foods that help prevent an inflammatory response from happening in the first place. And what a marvelous selection of sweet and savory plant foods we have to choose from: think of red, purple, and blue berries; red and purple grapes; apples; kale; broccoli; yellow onions; juicy red tomatoes; and green scallions.
All these foods contain flavonoids and/or carotenoids, a broad class of chemicals that gives plants pigment. They are also especially high in anthocyanins and flavonols, subclasses of flavonoids that are related to lower levels of inflammation and oxidative stress.
Other anti-inflammatory foods include oily fish, nuts, flaxseed, flax oil, and leafy vegetables—because all these items are rich in omega-3 fatty acids.
Your body requires omega-3s to reduce inflammation and keep telomeres healthy. Omega-3s help form cell membranes throughout the body, keeping the cell structure fluid and stable. In addition, the cell can convert omega-3s into hormones that regulate inflammation and blood clotting; they help determine whether artery walls are rigid or relaxed.
A general consensus seem to be a daily dosage of at least 1,000 milligrams of a mixture of EPA and DHA, which is similar to the low dose tested in the Ohio State study.
Telomere research suggests that you should make consumption of omega-3s a priority. But you also have to keep an eye on the balance between your omega-3s and omega-6s, because the typical Western diet tilts us more toward omega-6s than omega-3s. To keep your omegas in balance, we suggest that you keep eating healthy, unprocessed foods like nuts and seeds—but dramatically reduce your consumption of fried foods, packaged crackers, cookies, chips, and snacks, which often contain oils made with high amounts of omega-6s, as well as saturated fats, which are a risk factor for cardiovascular disease.
Homocysteine levels go up with aging, and correlate with inflammation, wreaking havoc on the lining of our cardiovascular system to promote heart disease.
If you have especially high homocysteine, this is one of the cases where a vitamin pill might help—B vitamins (folate or B12) appear to reduce homocysteine.
Oxidative stress—that dangerous condition that occurs when there are too many free radicals and not enough antioxidants in your cells—damages this precious sequence, especially its GGG segments. Free radicals take aim at that big juicy row of GGG pieces, a particularly sensitive target. After free radicals have their way, the DNA strand is broken; the telomere gets shorter faster.
Vitamin C and other antioxidants (like vitamin E) are scavengers that gobble up free radicals, preventing them from harming your telomeres and cells. People with higher blood levels of vitamins C and E have longer telomeres, but only when they also have lower levels of a molecule known as F2-isoprostane, which is an indicator of oxidative stress. The higher this ratio between blood antioxidants and F2-isoprostane, the less oxidative stress there is in the body. This is just one of the many reasons you should eat fruits and vegetables every day; they offer some of the best sources of antioxidant protection. To get sufficient antioxidants in your diet, eat plenty of produce, especially citrus, berries, apples, plums, carrots, green leafy vegetables, tomatoes, and, in smaller portions, potatoes (red or white, with the skin on). Other plant-based sources of antioxidants are beans, nuts, seeds, whole grains, and green tea.
In general, antioxidants from food are typically better absorbed by the body and may have more powerful effects than supplements.
Here’s a frame-by-frame shot of what happens when you swallow sugary soda, or “liquid candy”: Almost instantaneously, the pancreas releases more insulin, to help the glucose (sugar) enter cells. Within twenty minutes, glucose has built up in the bloodstream and you have high blood sugar. The liver starts to turn sugar into fat. In about sixty minutes, your blood sugar falls, and you start thinking about having more sugar to pick you back up after the “crash.” When this happens often enough, you can end up with insulin resistance.
Higher levels of vitamin D in the blood predict lower overall mortality rates. Some studies find that vitamin D is related to longer telomere length, more so in women than men, and other studies do not find a relationship.
After the period of drinking coffee, the patients had significantly longer telomeres and lowered oxidative stress in their blood than the control group. Further, in a sample of over four thousand women, those who drank caffeinated coffee (but not decaffeinated) were likely to have longer telomeres. More reasons to enjoy the aroma of your morning coffee brewing.
Inflammation, insulin resistance, and oxidative stress are your enemies. To fight them, follow what’s been called a “prudent” pattern of eating: Eat plenty of fruits, vegetables, whole grains, beans, legumes, nuts, and seeds, along with low-fat, high-quality sources of protein. This pattern is also known as the Mediterranean diet. Consume sources of omega-3s: salmon and tuna, leafy vegetables, and flax oil and flaxseeds. Consider supplementation with an algae-based omega-3 supplement. Minimize red meat (especially processed meat). You might try to go vegetarian for at least a few days each week. Eliminating meat can benefit your cells as well as the environment. Avoid sugary foods and drinks, and processed foods.
Chemical
Which chemicals might unnaturally lengthen telomeres too much? Exposure to dioxins and furans (toxic by-products that are released through various industrial processes and that are commonly found in animal products), arsenic (common in drinking water and some foods), airborne particulate matter, benzene (exposure occurs via tobacco smoke as well as gasoline and other petroleum products), and polychlorinated biphenyls (or PCBs, a class of banned compounds that is still found in some high-fat animal products) is associated with longer telomere length. What is so interesting is that some of these chemicals have also been linked to cancer risks.
Relationships and environment
Our physiological responses moment to moment are more synced with our partner’s than we may realize. For example, in one study examining couples having both positive and stressful discussions in the lab, heart rate variability followed the pattern of the other partner with a slight
We are interconnected in ways we cannot see, and telomeres reveal these relationships. We are affected by the toxic stress of discrimination. We are affected by toxic chemicals. We are affected in more subtle ways, by how we feel in our neighborhood, by the abundance of green plants and trees nearby, and by the emotional and physiological states of those around us. When we know how we are affected by our surroundings, we can begin to create healthful, supportive environments in our homes and our neighborhoods.
How could a parent’s education level affect the telomeres of her developing baby? The answer is that telomeres are transgenerational. Parents can, of course, hand down genes that affect telomere length. But the really profound message is that parents have a second way of transmitting telomere length, known as direct transmission. Because of direct transmission, both parents’ telomeres—at whatever length they are at the time of conception in the egg and sperm—are passed to the developing baby (a form of epigenetics).
Animal research suggests that modest protein deprivation in pregnancy causes accelerated telomere shortening in the offspring in a number of tissues, including the reproductive tract, and can lead to earlier mortality.
