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Published on: May 17, 2014
by Women’s Brain Health Initiative:
Throughout history, humans have demonstrated a fascination with the topic of aging. Stories about the Fountain of Youth abound. Tales have been told by various cultures across many centuries that anyone who drinks or bathes in the waters of the Fountain of Youth will restore their youthful health and vigor. This fascination with the Fountain of Youth myth demonstrates the high motivation to identify factors that can reverse, or at least slow down, the process of aging.
“The process of aging itself cannot be avoided, and is an important, natural part of life,” explains Jens Pruessner, an associate professor and researcher at McGill University. He goes on to provide hope, suggesting that “perhaps something can be done about age-related illness and disease, though.” So, we can’t avoid getting older but there might be ways to stay healthier and avoid sickness and disease as we age. Pruessner, the Director of the McGill Centre for Studies in Aging, leads research looking at one of the main factors identified so far that leads to accelerated aging and increased risk of disease – stress.
The Discovery of Telomeres
To understand the role of stress on health as we age, we first need to consider what is happening in the body as we age that leads to sickness and disease. Both the aging process itself and age-related diseases have to do with something called telomeres which are molecular caps at the end of our chromosomes, much like the caps on the ends of shoelaces. Research by Nobel Prize winner Elizabeth Blackburn showed that every time a cell divides and duplicates our DNA information, a little bit of this telomere gets chopped off. So, telomeres get shorter and shorter each time the cells divide. When telomeres are used up, the cell can no longer divide and then it dies. “So telomeres are kind of like an internal clock inside our cells,” explains Pruessner, “giving each cell a certain life span.”
Clearly, there is a consistent decline of telomeres with normal aging. However, there is significant variation in how quickly telomeres are used up and cells die. Some people’s telomeres get shorter sooner than they should given their age; they show signs of accelerated aging. Why? Among the various environmental factors that can contribute to accelerated shortening of telomeres, stress stands out as one of the most important.
Telomeres Provide Evidence of Accelerated Aging
A team of researchers from University of California – San Francisco conducted a study comparing the telomere length of two groups of women: (1) women with healthy children; and (2) women with a chronically ill child. As telomere length was measured over time, the study revealed that the women with chronically ill children, dealing with high levels of chronic stress, had telomere lengths equivalent to someone 10 years older. Chronic stress had accelerated the aging of their telomeres by a decade.
The research on telomeres makes it clear that stress leads to accelerated aging that affects cells throughout your body. But, what exactly is stress? Pruessner explains, “Stress is typically defined as an increased demand on the individual brought on by a change in the environment. Our bodies react to this change in demand with increased activity in a number of systems that allow us to mobilize energy to cope with the challenge or threat.”
Our physiological system reacts, releasing adrenaline as we experience the ‘fight or flight’ response. Our endocrine system also reacts by releasing a hormone from the adrenal cortex, cortisol, providing a second energy boost to help with coping during acute stress. In the long term, however, it is the hormone cortisol that has been linked to an accelerated shortening of the telomeres and thus to accelerated aging, and the possibility of sickness and disease.
The Impact of Cortisol
The effects of stress, and exposure to the stress hormone cortisol, have also been studied by Robert Sapolsky of Stanford University. He discovered that many disease states are associated with high amounts of cortisol being released and that the longer the excessive cortisol release goes on, the more the brain and body are affected. Sapolsky’s work concentrated on the hippocampus, an important part of the brain that is associated with memory formation and learning; it is a part of the brain that is known to shrink with dementia.
“We know that women are more prone to age-related disease and that this imbalance becomes even more pronounced when you look at brain diseases, specifically Alzheimer’s, which is the leading neurodegenerative disease in old age,” states Pruessner.
Women Respond More Strongly to Social Stress
Stress might be directly related to this increase in chronic illness in women in the later parts of their lives. Pruessner refers to two studies that provide possible explanations for this. In one study, women responded more strongly to certain types of stress, namely social stress. Their bodies showed signs of higher stress, including increased release of cortisol, in response to stressful situations that involved a social component (e.g., presenting in front of an all male audience) compared to men’s lower responses to the reverse situation (e.g. presenting to an all female audience).
Later studies revealed that women’s responses to stress also vary depending on the amount of estrogen present in their bodies. Women in the follicular phase of their menstrual cycle, when estrogen levels are highest, or women using estrogen-containing oral contraceptives, show lower levels of cortisol in response to stress, compared to women in the luteal phase of their menstrual cycle when estrogen levels are lowest. So, estrogen buffers the effects of stress, reducing the amount of cortisol released.
“Of course that is only true as long as you have estrogen in your system. This could explain why we see a shift to more women than men experiencing age-related disease, particularly brain disease, after 50 years of age, because that’s typically when women enter menopause,” explains Pruessner.
The Role of Estrogen
Pruessner shares an interesting, little known fact about estrogen: “Both men and women have estrogen in their bodies; while estrogen is produced by the ovaries in women, in men, part of the testosterone produced by the testicles gets converted to estrogen. This is probably because this hormone serves important functions, especially in the brain.” Women only have more estrogen than men until menopause. After menopause, women’s estrogen levels drop dramatically because their ovaries stop producing estrogen, while in men, the conversion of testosterone to estrogen continues life-long.
So, if estrogen can help minimize the effects of stress by decreasing the cortisol response and protecting the hippocampus and other parts of the brain, one might expect hormone replacement therapy (HRT) using estrogen to prevent cognitive decline in post-menopausal women. That is, in fact, what has been observed. Multiple studies of hormone replacement therapy supplementing estrogen after menopause have shown positive impacts on brain health, i.e. reduced risk of dementia, larger hippocampal volume, and increases in cognitive function.
All of this is a powerful argument that estrogen should be very good as a treatment, however there has been “quite a controversy surrounding the use of hormone replacement therapy including estrogens,” Pruessner points out. A study that was published in 2002 by the World Health Organization showing an increased risk of breast cancer, blood clots in the veins, and bladder infection with HRT recommended that women stop using HRT. Not surprisingly, use of HRT has plummeted dramatically since.
That World Health Organization recommendation has been revisited since, in numerous articles. The latest analysis points to the need for further research before reaching a final conclusion about the risks versus benefits of HRT. It will be important to consider different forms of HRT and dosages. The original study looked at one particular type of estrogen therapy which was derived from horse hormones and it is thought that that type of HRT might have at least in part contributed to the negative effects. Whether estrogen is used on its own, or in combination with progesterone, is known to have a significant effect on outcomes as well. And the timing of HRT administration (i.e. patient’s age during treatment), and the amount and the frequency with which HRT is used, all seem to play a role as well.
“The more you are able to mimic the naturally occurring menstrual cycle, in giving dosed HRT, the more you might be able to avoid any of the negative effects and just gain the beneficial effects. And I think this is where research is currently heading,” says Pruessner.
Reducing Stress Naturally
A lot can be done to minimize stress, and reduce cortisol in your body, naturally. Cortisol regulation is coordinated by the brain so your cortisol levels are affected by the way you approach your life and your perception of potentially stressful situations. Pruessner points out that “if you don’t perceive something as so stressful then you will not get the same amount of cortisol released in response to that situation.”
So how do you avoid perceiving situations as stressful? Pruessner recommends activities that allow your mind to rest and recuperate, for example meditation or yoga, which have been shown to reduce stress. The important thing is for people to find a stress-reducing activity that works for them. Jogging outdoors is Pruessner’s personal choice for stress reduction. Pruessner describes, “what I find great about jogging is that while you’re obviously exercising your body, you are allowing your mind to rest as well; you let go, you’re not working on anything. To me, the mind part of jogging is as powerful as the physical part.”
Unfortunately no one has found the Fountain of Youth to reverse the effects of aging. “It’s not quite that easy,” Pruessner says. Then he jokes, “If you find that fountain, do let me know. I’d like to take a bath myself.” In the meantime, remember that taking steps to reduce stress in your life can certainly help to keep your body and brain healthy longer, giving you at least in part the benefits of the Fountain of Youth.
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