Cell division – the constant replacement of old, worn-out cells with new healthy ones – is what keeps us alive. Yet our cells have only a limited ability to replicate and renew themselves over the course of our lives. Inside the nucleus of each cell, our genes are arranged along twisted, double-stranded molecules of DNA called chromosomes, the blueprint of our physical being. At the end of our chromosomes are bands of DNA called telomeres, cap-like structures that have been compared with the plastic tips on shoelaces. They keep the ends of chromosomes from fraying or sticking to each other, preventing the mutation or loss of genetic information during the very fragile process of cell division. Ultimately, telomeres play a key role in maintaining the stability of our genetic code over our lifetime and may hold the secret to aging. It’s no wonder that telomeres have been referred to as the “longevity gene.”
Telomeres allow cells to divide without losing genes. They are longest when we are first born, and shorten over time as our cells continually divide. As they grow shorter, our cells degrade. Once telomeres reach a critically short length, our cells lose their ability to replicate and begin to die without replacement. In fact, every cell in our body has a limited number of times it can replace itself before it is pre-programed to die (apoptosis). Ultimately, telomere shortening is associated with aging, inflammation, chronic disease, cancer and mortality. Telomeres can be thought of as a kind of “molecular clock” that starts its countdown from the moment we’re born.
Mounting scientific evidence suggests that telomere length is linked to longevity. In white blood cells, the length of a telomere declines from 8,000 base pairs in newborns, to 3,000 base pairs in adults, to finally reach a low of 1,500 in elderly people. (For the sake of comparison, an entire chromosome has about 150 million base pairs.) Each time it divides, the average cell loses between 30 to 200 base pairs from the ends of its telomeres. A cell can normally divide about 50 to 70 times, with telomeres getting progressively shorter, before it dies. Certain cells, like those found in our skin, hair and immune system, are most affected by telomere shortening – and the signs of aging – since they reproduce so frequently. Alternately, telomeres do not shorten in tissues where cells do not divide, such as heart muscle. And a few cells — namely adult stem cells as well as sperm and egg cells — are not limited by this process. These cells have an enzyme called telomerase that can rebuild telomeres when they get too short. This process is hijacked by cancer cells, which are said to become “immortal” by turning on telomerase.
Importantly, telomere length is not consistent. Instead, it varies between individuals, organs, cell types, and even between chromosomes. Telomeres are longer in women than men, mirroring the difference in lifespan between the sexes. Differences in telomere length also exist between ethnicities — African Americans generally have longer telomeres than Caucasian Americans, for instance. Yet, the steady decline in telomere length over the lifespan of an organism is universal. It is also true that telomere shortening accelerates with the onset of disease.
A variety of factors are known to prematurely shorten telomeres – including heredity, environment and lifestyle choices. One of the most influential of these factors is oxidative stress. Indeed, research confirms that smokers who have an increased oxidative burden also have decreased telomere lengths. Another striking demonstration of the effect of oxidative stress on telomere length comes from a study of 4,117 female participants in the famous Nurses’ Health Study (originally established in 1976, and continuing to this day). This research found that women under the age of 50 who slept less than 6 hours per night had significantly shorter telomeres than similar women who slept at least 9 hours. Shortened sleep is associated with decreased melatonin, a critical antioxidant. Thus, one consequence of shortened sleep duration is the reduced antioxidant effects of melatonin which increases the oxidative damage to telomeres.
Inflammation, another consequence of sleep deprivation, is also correlated with shortened telomeres. One characteristic of inflamed tissue is cell proliferation, with this increased cell turnover shortening our telomeres. If inflammation is widespread, the resulting chromosomal instability can leave the tissue vulnerable to dysfunction. It is suggested that telomeres may represent the missing link between chronic inflammation and chronic disease, including cardiovascular disease and cancer. It also suggests that a person in their 30’s or 40’s suffering with high levels of inflammation or oxidative stress may already be experiencing premature cellular aging.
Psychological stress also impacts telomeres. Adverse childhood events correlate with shortened telomeres in adulthood, with the greater number of adverse events directly proportional to the degree of telomere shortening. Depressive symptoms in young adults are also longitudinally associated with shorter telomeres. The fact that various forms of stress during childhood are associated with shortened telomeres may indicate that childhood is a particularly sensitive time for telomere reduction. Marital status, an indicator of social support and connectedness, is also correlated with telomere length: research indicates that unmarried individuals have shorter telomeres than their age-, gender- and ethnically-matched married counterparts. Pioneering biologist Hans Selye, who first described how rats, subjected to long-term stress, became chronically ill in the 1930’s wrote: “Every stress leaves an indelible scar, and the organism pays for its survival after a stressful situation by becoming a little older.”
Ground-breaking research in the 1980’s found that an enzyme called telomerase can slow, stop or even reverse the telomere shortening that happens as we age. In young cells, telomerase keeps telomeres from wearing down too much (although eventually, even telomerase declines, just like telomeres). Essentially, telomerase acts like an anti-aging enzyme. This discovery was so important that the 2009 Nobel Prize in Medicine was given to pioneers Elizabeth Blackburn, Carol Greider and Jack Szostak for their discovery of how chromosomes are protected by telomeres and the enzyme telomerase.
Since telomeres were first discovered, hundreds of studies have explored the link between telomere length and heart disease, diabetes, cancer, Alzheimer’s disease and emotional stress. After her Nobel Prize win, Blackburn began to collaborate with Elissa Epel, a psychologist who studies chronic stress. One of their first projects focused on mothers who were the primary caregivers of children suffering with chronic disease to examine the relationship between their state of mind and the state of their telomeres. Compared with the mothers of healthy children, those with sick ones had shorter telomeres and less telomerase, and the longer they had been caring for the children, the shorter their telomeres were. In fact, the most stressed women in the study had telomeres that translated into an extra decade of aging compared to those who were least stressed. This study provided startling evidence that connects the stress of real life with the molecular mechanics inside our cells. It was also the first indication that stress doesn’t just damage our health – it literally ages us. These findings triggered an explosion of new research that has since linked perceived stress to shorter telomeres in long term caregivers of Alzheimer’s patients, victims of domestic abuse and early life trauma, and people with major depression and post-traumatic stress disorder. Research has also made progress toward identifying a mechanism of action. Studies show that the stress hormone cortisol reduces the activity of telomerase, while oxidative stress and inflammation – the physiological fallout of psychological stress – appear to erode telomeres directly.
A meta-analysis of 24 studies involving over 40,000 participants found that those in the bottom third of telomere length had a 50% higher risk of cardiovascular disease than those in the top third. Another study among over 2,000 healthy Native Americans revealed that those with the shortest telomeres were more than twice as likely to develop diabetes over the next five-and-a-half years, even taking into account conventional risk factors such as body mass index and fasting glucose.
Finally, the clinical significance of telomere shortening and cancer was illustrated in a 10 year study, published by the Journal of the American Medical Association, which demonstrated a direct correlation between shortened telomeres and both an increased risk of developing cancer and increased risk of dying from cancer — especially cancer of the lung, breast, prostate, and colon. Indeed, all four of these cancer sites have highly proliferative epithelial tissues whose rapid rate of cell division prematurely shortens telomere length. Specifically, short telomere length at baseline was associated with a 3-fold increased risk of cancer and a 2-fold increased risk of cancer mortality. In another analysis of patients with Hodgkin’s lymphoma, those individuals with shortened lymphocyte telomeres before treatment were at significantly higher risk of developing secondary cancers.
While most research to date on telomeres has focused on the negative impact that their shortening has on longevity, a few studies have begun to examine the ability of healthy lifestyle choices to lengthen telomeres.
A pivotal pilot study by Dean Ornish published in the Lancet followed 35 men with low-risk prostate cancer and assessed the impact of a comprehensive lifestyle change program on telomere length. The lifestyle program consisted of a low-fat (10% of calories from fat), whole-foods, plant-based diet high in fruits, vegetables, unrefined grains, and legumes and low in refined carbohydrates; moderate aerobic exercise (walking 30 min/day, 6 days/week); stress management (gentle yoga-based stretching, breathing, meditation, imagery, and progressive relaxation techniques 60 min/day, 6 days/week), and a weekly group support session. Their diet was supplemented with soy (one daily serving of tofu plus 58g of a fortified soy protein powdered beverage), fish oil (3g daily), vitamin E (100 IU daily), selenium (200 mcg daily), and vitamin C (2g daily). Results found that comprehensive lifestyle intervention was associated with increased telomere length, compared to the control group whose telomere length declined. Because of the relatively small number of patients, it must be emphasized that these findings are preliminary.
A cross-sectional analysis of 5,862 women in the Nurses' Health Study also assessed the relationship between healthy lifestyles and telomere length. The five areas of lifestyle that were defined as healthy, low-risk practices included: not currently smoking, maintenance of a healthy body weight (BMI 18.5 – 25 kg/m2), regular moderate or vigorous physical activities (>150 minutes/week), moderate alcohol intake (1 drink/week to <2 drinks/day), and eating a healthy diet (higher intakes of vegetables, fruit, nuts, soy, cereal fiber, chicken, and fish with low consumption of red meat and trans or saturated fat). While none of the individual low-risk factors on their own was associated with telomere lengthening, women who embraced all five lifestyle practices saw their telomere length increase 31% while women who adhered to four of the practices had 23% longer telomeres.
Interestingly, NASA believes that lengthy space travel may also age people faster than those living on earth and is monitoring how the telomeres of astronauts (and twin brothers) Scott and Mark Kelly change over time. Scott spent nearly a year in space, orbiting Earth in the Space Station, about four times longer than Mark. NASA is evaluating whether extended exposure to radiation and reduced gravity accelerates the aging process.
Cellular aging – or senescence – describes a form of “exhaustion” that occurs over time until cells are no longer able to divide and carry out normal cellular activity. A substantial amount of scientific data suggests that the aging of individual cells plays a central role in the general decline of our muscle function, blood flow and metabolism which occurs as we grow older. Understanding cellular aging and the role that telomeres play will not only help unlock some of the mysteries of “healthy” aging, but may also help us understand and prevent many age-associated illnesses and diseases.
Importantly, telomere shortening does not appear to be written in stone. Stress management, sufficient sleep, proper diet and exercise are not only foundational strategies for living well, but seem to also positively impact telomere length. Indeed, telomere dynamics is one more proof-point in a growing list that validates a whole-person, lifestyle-based approach to health, vitality and longevity.