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Epigenetics and Aging
The Impact from Our Ancestors
People will not look forward to posterity, who never look backward to their ancestors.
Edmund Burke, Reflections on the Revolution in France, 1790
While most of this book will explore various factors that impact aging over which we have significant influence, the complete story of aging begins before we are even conceived. In this chapter we will explore those influences originating in our immediate ancestors that affect gene expression and impact aging in us. While we can do nothing to change history and the genetic material with which we were born, we can through healthy choices not only alter our genetic expression and thus impact our own health but also pass those changes down to our children, grandchildren, and great-grandchildren, impacting their health as well.
Every cell of our body that contains a nucleus contains the same genetic information—deoxyribonucleic acid, or DNA (with the exception of individuals with extremely rare disorders). Yet bone cells are different from skin cells, which are different from muscle cells, which are different from the cells in our eyes that transform light into electrical energy so we can see or the cells on our tongues that transform chemical signals into electrical ones so we can taste. Yes, all the cells in a person’s body have the same DNA, but the DNA is expressed differently, resulting in wide diversity in the shape, structure, and function of the various types of tissues throughout the body.
Our DNA is like a vast library of information with instructions on how to build everything the body needs. But each cell type opens only the books (genes) in the library that contain the information those cells need to do their job. Thus, cells in the stomach do not access the information on how to make bone, and cells in the brain don’t access the information on how to make blood cells, and so on. All the information is there in the library (chromosomes in the nucleus of each cell), but cells open only the books (genes) that have the information they need. This means there must be some instructions directing the cells on which books (genes) to access and use.
It was in 1957 that researcher Conrad Wadddington first made this observation and hypothesized that there must be some set of instructions that sits above the DNA instructing the DNA on which genes to turn on (express) and which genes to turn off (not express). He coined the term epigenetics—epi means above as in epidermis (the top layer of your skin), and genetics refers to the DNA. So epigenetics means the chemical instructions that direct the access and usage of the information contained within the DNA.
DNA, though incredibly small, is the massively huge database of information in which the instructions on how to build every part of our bodies are stored. Imagine a zipper, two rows of teeth that interlock. Now imagine that zipper is very long—miles long. It is zipped, then sections are wrapped around spools, and those spools are packed tightly together. This would be similar to how our DNA is stored. Each tooth on the zipper represents a DNA molecule. The molecules are organized in a way to create coded information from which our bodies are built. (Imagine the DNA molecules are letters of the alphabet, and they are organized to spell words that are put together in sentences containing building instructions for the body.) Just as there are two sides to a zipper, there are two strands of DNA that zip together, then wrap around histone molecules, which are packed tightly together to form our chromosomes. But in order to read the code the zipper must unpack, unwind, and unzip. DNA expression is modified by either enhancing or impairing the unpacking, unwinding, and unzipping.
There are various molecules that can attach to the DNA and influence its expression at these various points. For instance, methyl groups can attach directly to the DNA strand, and when this happens the DNA in that region is locked down. This would be like getting a shirttail caught in your zipper—the zipper cannot unzip. Methyl groups, therefore, when attached to the DNA strand, shut down the expression of the DNA in the region where they attach. Conversely, any gene that had methyl groups removed would experience an increase in expression. Environmental factors, life experiences, and even the thoughts we think can impact how our DNA is being expressed. And when we have children we not only pass along our DNA sequences but also the epigenetic instructions specifying which genes are turned on and which genes are shut down.
Smoking, Famine, and Grandchildren
Researchers in Sweden discovered that men who began smoking before age eleven had altered genes carried on their Y chromosome that caused their grandsons to have greater likelihood of obesity than if they had not smoked. And individuals who in their childhood (before puberty) experienced a short food supply had altered DNA expression such that the men conferred greater mortality risk to their grandsons and the women conferred greater mortality risk to their granddaughters. This means if you are a man and your grandfather (or if a woman and your grandmother) experienced a significant famine in their childhood, then you began life with a greater risk of dying young than if your grandparent had a normal food supply.1
Low-Calorie Diet during Pregnancy
Another provocative study examined children born in the Netherlands during WWII when there was a severe food shortage and whose mothers averaged about five hundred calories of food intake per day. These children grew up to have higher rates of obesity, diabetes mellitus type 2, and other metabolic problems such as hypercholesterolemia than their siblings (of the same parents) who were born when normal amounts of food were available. Genetic examination found that the metabolically compromised individuals had 5 percent fewer methyl caps on one specific gene (IGF2). This would result in an increased expression of this specific gene. The researchers concluded that this gene is involved in food metabolism, and the increased expression resulted in these individuals extracting more energy from food than their siblings.
What appears to have happened is that when these individuals were in utero during the food shortage, a signal was sent to the developing fetus that there were not many nutritional resources in the world. This low-energy input resulted in fewer methyl caps attached to gene IGF2, and these individuals were born genetically programmed to get more energy out of food. But the war ended and food supply normalized, and with normal food intake these individuals experienced greater rates of obesity, diabetes, and other metabolic problems—all of which, as we will see in later chapters, accelerate aging and increase the risk of dementia and early demise.2 Though we cannot alter the conditions of our birth, we can choose to alter our dietary patterns to conform to our individual ability to extract energy from food and thereby avoid or resolve obesity, diabetes, and hypercholesterolemia, slow our aging, and reduce our risk of dementia.
Smoking, Pregnancy, and Epigenetics
People have known for several decades that smoking during pregnancy is damaging to the developing fetus and increases the risk of smaller babies, learning and behavior problems, sudden infant death syndrome, and mental illness.3 But in 2016 researchers discovered that smoking while pregnant has much more devastating effects on the genetic expression of the child than imagined. Smoking while pregnant epigenetically alters more than six thousand genes, and nearly three thousand of these alterations persist into later life. Some of these altered genes have been implicated in cleft palate, asthma, and contributing to various cancers, including lung, colorectal, and liver.4 At least one study found that girls who were exposed to tobacco smoke in the womb were two to three times more likely to become nicotine addicted if exposed to tobacco later in life than girls not exposed to tobacco smoke in utero.5 This means that mothers who smoked while pregnant altered the reward pathways in the brains of their daughters, making them more vulnerable to nicotine addiction later in life. And as I will document later in this book, tobacco use accelerates aging and contributes to increased risk of dementia.
Alcohol, Pregnancy, and Epigenetics
Likewise we have known for generations that heavy alcohol consumption while pregnant increases the risk of all types of health problems—from fetal alcohol syndrome with multiple organ defects to increasing risks of mental illness.6 Many of these problems are a result of epigenetic modification and accelerate aging later in life. But what if a woman drank only one alcoholic beverage per week while pregnant? Would such a small quantity of alcohol have an impact on her unborn child? The answer appears to be yes. Children born to women who drank one alcoholic beverage per week had smaller heads, were shorter, and had more behavior and emotional problems later in life than those whose mothers did not drink.7 Again, these effects occur through epigenetic changes, and as we will see in later chapters, unresolved emotional stress accelerates the aging process.
If you find the taste of alcohol particularly enjoyable, perhaps your mother drank while pregnant with you. Animal research has documented that if a mother drank alcohol while pregnant, epigenetic modifications occurred in the genes of her offspring that code for taste, and her children would experience that alcohol tastes better than if she had not drank while pregnant.8 As we will discover in later chapters, heavy alcohol use accelerates aging and increases risk of dementia.
Air Pollution, Pregnancy, and Epigenetics
Dr. Bradley Peterson and his fellow researchers discovered that exposure to air pollution while pregnant impacts brain development. They found a dose-dependent effect of the concentration of air pollution on the developing fetal brain that altered white-matter tracks in the left hemisphere, resulting in increased risk of attention deficit hyperactivity disorder (ADHD) in the offspring. This means the greater the exposure to polycyclic aromatic hydrocarbons (the pollution from burning fossil fuels), the greater the damage to the white-matter tracks and the more likely a person will experience ADHD later in life.9 ADHD impacts the ability to organize, plan, self-restrain, and complete tasks. Those with untreated ADHD have higher rates of substance use problems, more relationship conflicts, and experience greater stress from routine life activities—all of which accelerate aging and increase the risk of dementia.
Mother’s Thinking While Pregnant and the Fetal Brain
Not only do diet, alcohol, tobacco, and pollution impact our genetic expression, but also the mother’s thinking patterns and stress levels epigenetically alter gene expression in the developing fetal brain, increasing the risk of depression and anxiety later in life. One study of more than four thousand mothers and their children who were followed for eighteen years found that if the mother had a pattern of pessimistic, negative, and depressive thinking while pregnant it increased the risk of her child developing depression eighteen years later by 21 percent.10 This association remained after accounting for other maternal and offspring risk factors for depression. And those with a history of depression have a higher risk of developing dementia than those who have not had depression.
Another study found that if a mother is highly stressed while pregnant, which may be no fault of her own, then her child will be born with a brain more vulnerable to anxiety and depression. A nineteen-year-old woman whose husband gets deployed into combat will be stressed. A twenty-five-year-old woman whose mother gets diagnosed with late-stage cancer will be stressed. The increased stress may not be due to unhealthy thinking patterns in the mother. But for whatever reason, if a woman is highly stressed during pregnancy, her stress hormones (glucocorticoids) will cross the placental barrier, cross the developing fetal blood-brain barrier, and epigenetically alter the braking mechanism in the developing fetal-stress circuitry (amygdala). This results in a child born with a more sensitive anxiety circuitry and an impaired braking mechanism to calm the anxiety circuitry. Such children are born more anxiety prone and less capable of calming themselves than if their mothers had not been highly stressed during pregnancy.11 As we will explore in later chapters, unremitting anxiety, stress, and depression increase inflammatory cascades, which accelerate aging and increase the risk of depression and dementia.
Early Childhood and Epigenetics
What we have learned thus far is that before we are born factors impact our DNA and contribute to the aging process. Such factors work together to establish our starting point, our biological and genetic state at birth. However, our genes and thus our bodies and brains remain changeable based on experiences throughout our lives. This is great news because regardless of our starting point we are not stuck. We can experience healthy events and make wise choices that will alter our genes in positive ways, bringing healthy benefits and slowing the aging process. Conversely, ongoing unhealthy life events or choices will only add to the damage.
It has been told that the Holy Roman Emperor Fredrick II of Germany wanted to discover the original language spoken by Adam and Eve. He therefore conducted an experiment in which infants were raised by surrogates who were instructed to feed and change the babies but not to hold, cuddle, speak to, or show any affection or ongoing attention to them. The infants were exposed to only the most minimal contact to provide physical nurturance. The hypothesis was that if there was a primal language encoded within humanity, these infants, not influenced by caregivers, would speak it. Would it be Hebrew, Greek, Latin, or something else? The emperor never found out because without touch, without human contact, without interaction, love, and affection—all the infants died.12
While Frederick’s experiment did not uncover a primal human language, it did reveal the importance of love, affection, human touch, and contact in early childhood. These benefits appear to be important to nonhumans as well. Animal research compared pups born of mothers who regularly licked and groomed them to pups who were neglected by their mothers. Pups without attentive mothers had epigenetic modification of their amygdala (fear circuits) such that they were more anxious and socially impaired than the pups of attentive mothers. What this implied was that the licking and grooming—the affection—was exerting a positive influence on genetic expression and brain development.
However, researchers realized that perhaps the impairments in the amygdala of the neglected pups were genetically programmed to start with and that their mothers were neglectful because they suffered with the same genetic defect. In a follow-up experiment they took the pups born of neglectful mothers and placed them with attentive mothers who licked and groomed them regularly—and the result? Their brains developed normally without any social impairment or increased activity in their anxiety circuits.13 What this means is that regardless of our starting point at birth our brains remain changeable; early childhood experiences can impact our genetic expression in positive ways and alter brain development.
Yes, childhood is a time of great vulnerability but also great opportunity. Healthy experiences epigenetically alter cellular and brain function in positive ways and lay a foundation for better health and longer life whereas negative experiences do just the opposite.
Child Abuse and Epigenetics
A study of forty-one Canadian men compared the gene expression of twenty-five who were severely abused to sixteen controls. The DNA from their hippocampi (the part of the brain involved in memory, new learning, and calming the stress response) was examined, and 362 epigenetic differences between the two groups were identified. The most significant differences were in genes that coded for neuroplasticity—the ability to change, adapt, and make new neurons and neuron-to-neuron connections. The abuse group had significant impairment in their brains’ ability to change and grow when compared to controls.14
In another study of over eight hundred people who were followed for thirty-two years, researchers discovered that severe childhood adversity markedly increased the risk of developing depression, diabetes, obesity, and hypercholesterolemia later in life.15 Multiple other studies document that children who experience severe neglect, physical or sexual abuse, or extreme poverty suffer as adults with higher rates of physical health problems (diabetes mellitus, asthma, obesity, hypercholesterolemia, cardiac disease), mental health problems (depression, anxiety, alcohol and drug problems), and relationship problems and die at a younger age than those who do not experience such childhood adversity.16 However, research has documented that individuals with trauma histories who participated in cognitive therapy experienced epigenetic changes that brought healing. Specifically, genes associated with the ability to make new neurons (neuroplasticity) were turned on and brain volume increased, and genes associated with calming the brain’s stress response were activated. Thus, these individuals were able to experience less emotional and physical stress with improved mental and physical health.17 This is very good news because regardless of our starting point in life we can make choices that can bring healing, slow aging, and lower our risk of dementia.
Other research has demonstrated the healing power of forgiveness, which is not letting someone off the hook or trusting an abuser or forgetting the past. Forgiveness is resolving the bitterness, resentment, anger, and frustration within oneself. Forgiveness is removing the psychological thorn that causes ongoing emotional pain and chronic activation of the body’s stress pathways. In other words, forgiveness heals the one who was wronged; it does not change the one who did wrong. For those who forgive, a history of significant life stress was not a predictor of poor mental health. In women who were abused by their spouses, it was those who not only set boundaries and put an end to the abuse but also forgave who experienced resolution of depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms.18 Forgiving those who wrong us is healing to us!
Memory and Epigenetics
In an interesting animal study, scientists engineered mice with a specific gene defect that caused memory and learning problems. They divided the mice into two groups (all with the genetic defect). The experimental group was exposed to an “enriched” environment for two weeks during their adolescence. A mouse-enriched environment would be a habitat with climbing apparatus, running wheels, toys, and other interesting textures and shapes. The control group was not exposed to such an enriched environment. It wasn’t surprising to the researchers that the mice with the enriched environment had better memory and could learn at a faster rate than the mice without the enriched environment.
What amazed the scientists was what happened to the next generation. The offspring of the control group were born with the genetic defect and grew up with the same memory and learning problems as the parents. But the offspring of the experimental group (mice exposed to an enriched environment) though born with the genetic defect had that defect epigenetically modified such that it did not cause memory and learning problems. These offspring had normal memory and learning even though they did not get an enriched environment during their adolescence. What this means is that the positive experiences in the adolescence of their parents altered the expression of the defective gene in a positive way so that their offspring were born with normal memory and learning.19
Regardless of our history we can make choices today that will result in positive health changes to our bodies and brains and thereby slow the aging process and reduce the risk of dementia. The evidence would seem to suggest that if we do this before we have children, not only will we benefit but so will our children and grandchildren. And as we will discover in subsequent chapters, even when healthy changes are implemented late in life they can produce dramatic results to slow, forestall, or even prevent the development of dementia.
LEARNING POINTS
- We are designed to adapt and change based on our life experiences. Therefore, our choices will either increase or decrease our dementia risk.
- Essentially every experience in life changes us; we not only form new memories but also our gene expressions and brain structures change, which result in either accelerated or slowed aging.
- While we cannot change history, we can make modifications in our lives today that will have a positive influence on our gene expression, brain development, health, and aging.
- Regardless of our starting point in life we can make choices that can bring healing, slow aging, and lower our risk of dementia.
- Resentment, anger, and bitterness activate the brain’s stress pathways, increasing inflammation and accelerating aging while undermining physical and mental health—all of which increase the risk of dementia.
- Forgiving others who have wronged us calms our internal stress pathways, reducing activation of the immune system, and results in better mental and physical health.
- Share with friends and family how our life experiences and choices epigenetically change us and that we pass those changes along to future generations.
- If you have a history of trauma consider cognitive therapy or other specific interventions to address the impact the trauma is having on you today. While you cannot change history, you can change how you react to that history today. Seek interventions that result in reduced activation of your brain’s stress circuitry.
- Evaluate your life history, whether you hold resentment, bitterness, or anger about any wrong done you, and choose to work through it so you can forgive and remove the emotional thorn from your heart. Consider professional therapy if needed.
- Fill your life with a variety of interesting and engaging activities that stimulate your interest and expand your imagination: art, music, crafts, bird watching, visiting national parks, and so on.