Clues to increased longevity in women vs. men

In the United States, the human life span has increased substantially in the past century, the product of better medical management and a slowing of biological aging. National studies of health biomarkers have demonstrated a deceleration of the aging process over time, and deaths from cardiovascular disease and stroke have declined. However, this positive increase in life span is offset by a potential increase in other diseases, such as obesity and diabetes. Moreover, longevity is associated with higher prevalence of Alzheimer’s disease and other dementias, both of which are more common in women than men.

Elissa Epel

“When we live longer, we are more likely to get dementia, so there is a sharp trade-off,” Elissa Epel, PhD, professor of psychiatry at the University of California, San Francisco, and director of the Aging, Metabolism, and Emotions Center and the Consortium for Obesity Assessment, Study and Treatment, told Endocrine Today. “Longevity, when not healthy, is not something people seek as a goal for their later years of life. It’s the health span, our years of healthy living, that we want to focus on and maximize.”

Due to a variety of complex factors, women in the U.S. live approximately 5 years longer than men, according to Epel, who is also co-author of The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer (Grand Central Publishing; 2017). Given this increased longevity, women can benefit from efforts toward making these years healthy and fulfilling.

Epel spoke with Endocrine Today about the various contributors to life span, approaches that might promote greater longevity, and ways to reach these years with optimal health.

What are some natural physiological advantages women have over me n when it comes to longevity?

Epel: Women have a biological advantage when it comes to aging. A fundamental aspect of human biology is that women have a longer life expectancy than men. The reasons women live longer are complex and due to both genetics and biology, such as female sex hormones, and behavioral differences.

When we examine biomarkers that indicate aspects of biological aging earlier in life, we see a female advantage as well in many indices. For example, women have a younger epigenetic clock. Women also have longer telomeres, a difference that appears to exist at birth.
At a simple level, we can see that part of this advantage is due to greater estrogen exposure, as shown by animal studies. In humans, there are not that enough studies on sex differences in aging mechanisms. Studies have started to look at hormones and reproduction, and the data are suggestive about the protective effects of endogenous estrogen on biomarkers of aging, but there are too few studies on this topic and the findings are mixed.

How much do differences in the length of telomere s, the nucleotide sequences that prevent deterioration of chromosome s, explain the longevity gap?

Epel: Telomere length alone does not explain the sex difference in longevity. However, it may be one factor adding to this gap. Women have longer telomere lengths, and shorter telomere length predicts earlier mortality. A new meta-analysis of telomere length and mortality showed that in the Swedish Twin Registry studies, having telomere length shorter by 1 standard deviation was associated with a 13% increased risk for earlier mortality. When comparing the lowest quartile to the highest quartile, there is a 44% higher hazard of early mortality in the short group. The strength of the relation between telomere length and mortality is similar for women and for men, so they are playing the same role of protection for both sexes. Levels of inflammation are also an important marker of aging and risk for earlier mortality, including in the very elderly. It is also interesting that telomere length is predictive in midlife but is not a good predictor of mortality for adults once they are aged 80 years or older.

We have a lot more to learn about the role of telomeres in our health during the lifespan, during childhood and in later years. The NIH is taking this seriously by putting funds into better telomere measurement and into understanding how they are affected by certain exposures and how much we can protect them with interventions.

How might sex hormones be a key to understanding longevity?

Epel: The difference in longevity by sex is not something scientists fully understand yet, but given this robust sex difference across cultures, it holds clues to understanding the basic biology of aging in humans. We know from basic research that estrogen can upregulate telomerase. In women, having one’s last child at a later age is related to both longer telomere length and longevity. Later age of menopause relates to longer telomeres in some studies but not others — this is a new area of inquiry that really demands further research.

We know little about the causes of sex differences in humans and need more research on how aging affects men and women differently. This becomes especially important because potential pharmacologic interventions to slow aging, as tested in worms and rodents, often work in one sex but not the other. We should not just shrug our shoulders about this, but dive into understanding it in a serious way. This is a promising opportunity for discovery.

Are there certain behaviors that can increase telomere length or slow its decrease?

Epel: Having a long reproductive life, a later menopause, seems important. However, that is not under our personal control that we know of. It is surprising that there is so little research on women’s reproductive health and aging, but there is a history to this: For a long time, research did not include female animals, and that has left us with male-oriented therapies that don’t work as well in women and little information about how the role of reproductive hormones. But this gap in research — and the robust sex gap in longevity — shines light on a big opportunity for scientists to learn useful discoveries on how to promote healthy longevity.

There are many things individuals can do; we can control our rate of cell aging by engaging in those small healthy behaviors each day that are easy to do, yet add up over time to be very meaningful to our body. The same lifestyle factors — activity, nutrition, good quality sleep — that protect the heart and the brain are also associated with longer telomeres and lower inflammation. Better management of daily stress is critical. Exercise, a whole food diet and healthy behaviors can protect telomeres. On the other hand, we know it is equally important to avoid the things that speed up our cellular aging. This includes, for example, the chronic unrelenting stress that comes with poverty, discrimination, depression and unhealthy jobs with too much demand and lack of control that can lead to burnout, to which many women are exposed more than men.

Lastly, minimizing our exposures to factors outside of our body that impact telomeres is also important. This means avoiding processed food and minimizing toxic chemical exposures, like metals, pesticides and chemicals in plastics, which surround us. Air pollution is related to shorter telomeres in people and even in newborns. Some of these chemicals are endocrine disruptors, they act as mimics of our natural sex hormones, can block or exaggerate their effects, and are thought to contribute to diabetes and other diseases. This includes, for example, chemicals used in plastics, such as bisphenol A (BPA) and polychlorinated biphenyls (PCBs). – by Jennifer Byrne

For more information:

Elissa Epel, PhD , can be reached at 3333 California St., San Francisco, CA 94118; www.amecenter.ucsf.edu; email: elissa.epel@ucsf.edu.

Disclosure: Epel reports she is co-author of the book The Telomere Effect with Elizabeth Blackburn, PhD.

In the United States, the human life span has increased substantially in the past century, the product of better medical management and a slowing of biological aging. National studies of health biomarkers have demonstrated a deceleration of the aging process over time, and deaths from cardiovascular disease and stroke have declined. However, this positive increase in life span is offset by a potential increase in other diseases, such as obesity and diabetes. Moreover, longevity is associated with higher prevalence of Alzheimer’s disease and other dementias, both of which are more common in women than men.

Elissa Epel

“When we live longer, we are more likely to get dementia, so there is a sharp trade-off,” Elissa Epel, PhD, professor of psychiatry at the University of California, San Francisco, and director of the Aging, Metabolism, and Emotions Center and the Consortium for Obesity Assessment, Study and Treatment, told Endocrine Today. “Longevity, when not healthy, is not something people seek as a goal for their later years of life. It’s the health span, our years of healthy living, that we want to focus on and maximize.”

Due to a variety of complex factors, women in the U.S. live approximately 5 years longer than men, according to Epel, who is also co-author of The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer (Grand Central Publishing; 2017). Given this increased longevity, women can benefit from efforts toward making these years healthy and fulfilling.

Epel spoke with Endocrine Today about the various contributors to life span, approaches that might promote greater longevity, and ways to reach these years with optimal health.

What are some natural physiological advantages women have over me n when it comes to longevity?

Epel: Women have a biological advantage when it comes to aging. A fundamental aspect of human biology is that women have a longer life expectancy than men. The reasons women live longer are complex and due to both genetics and biology, such as female sex hormones, and behavioral differences.

When we examine biomarkers that indicate aspects of biological aging earlier in life, we see a female advantage as well in many indices. For example, women have a younger epigenetic clock. Women also have longer telomeres, a difference that appears to exist at birth.
At a simple level, we can see that part of this advantage is due to greater estrogen exposure, as shown by animal studies. In humans, there are not that enough studies on sex differences in aging mechanisms. Studies have started to look at hormones and reproduction, and the data are suggestive about the protective effects of endogenous estrogen on biomarkers of aging, but there are too few studies on this topic and the findings are mixed.

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How much do differences in the length of telomere s, the nucleotide sequences that prevent deterioration of chromosome s, explain the longevity gap?

Epel: Telomere length alone does not explain the sex difference in longevity. However, it may be one factor adding to this gap. Women have longer telomere lengths, and shorter telomere length predicts earlier mortality. A new meta-analysis of telomere length and mortality showed that in the Swedish Twin Registry studies, having telomere length shorter by 1 standard deviation was associated with a 13% increased risk for earlier mortality. When comparing the lowest quartile to the highest quartile, there is a 44% higher hazard of early mortality in the short group. The strength of the relation between telomere length and mortality is similar for women and for men, so they are playing the same role of protection for both sexes. Levels of inflammation are also an important marker of aging and risk for earlier mortality, including in the very elderly. It is also interesting that telomere length is predictive in midlife but is not a good predictor of mortality for adults once they are aged 80 years or older.

We have a lot more to learn about the role of telomeres in our health during the lifespan, during childhood and in later years. The NIH is taking this seriously by putting funds into better telomere measurement and into understanding how they are affected by certain exposures and how much we can protect them with interventions.

How might sex hormones be a key to understanding longevity?

Epel: The difference in longevity by sex is not something scientists fully understand yet, but given this robust sex difference across cultures, it holds clues to understanding the basic biology of aging in humans. We know from basic research that estrogen can upregulate telomerase. In women, having one’s last child at a later age is related to both longer telomere length and longevity. Later age of menopause relates to longer telomeres in some studies but not others — this is a new area of inquiry that really demands further research.

We know little about the causes of sex differences in humans and need more research on how aging affects men and women differently. This becomes especially important because potential pharmacologic interventions to slow aging, as tested in worms and rodents, often work in one sex but not the other. We should not just shrug our shoulders about this, but dive into understanding it in a serious way. This is a promising opportunity for discovery.

PAGE BREAK

Are there certain behaviors that can increase telomere length or slow its decrease?

Epel: Having a long reproductive life, a later menopause, seems important. However, that is not under our personal control that we know of. It is surprising that there is so little research on women’s reproductive health and aging, but there is a history to this: For a long time, research did not include female animals, and that has left us with male-oriented therapies that don’t work as well in women and little information about how the role of reproductive hormones. But this gap in research — and the robust sex gap in longevity — shines light on a big opportunity for scientists to learn useful discoveries on how to promote healthy longevity.

There are many things individuals can do; we can control our rate of cell aging by engaging in those small healthy behaviors each day that are easy to do, yet add up over time to be very meaningful to our body. The same lifestyle factors — activity, nutrition, good quality sleep — that protect the heart and the brain are also associated with longer telomeres and lower inflammation. Better management of daily stress is critical. Exercise, a whole food diet and healthy behaviors can protect telomeres. On the other hand, we know it is equally important to avoid the things that speed up our cellular aging. This includes, for example, the chronic unrelenting stress that comes with poverty, discrimination, depression and unhealthy jobs with too much demand and lack of control that can lead to burnout, to which many women are exposed more than men.

Lastly, minimizing our exposures to factors outside of our body that impact telomeres is also important. This means avoiding processed food and minimizing toxic chemical exposures, like metals, pesticides and chemicals in plastics, which surround us. Air pollution is related to shorter telomeres in people and even in newborns. Some of these chemicals are endocrine disruptors, they act as mimics of our natural sex hormones, can block or exaggerate their effects, and are thought to contribute to diabetes and other diseases. This includes, for example, chemicals used in plastics, such as bisphenol A (BPA) and polychlorinated biphenyls (PCBs). – by Jennifer Byrne

For more information:

Elissa Epel, PhD , can be reached at 3333 California St., San Francisco, CA 94118; www.amecenter.ucsf.edu; email: elissa.epel@ucsf.edu.

Disclosure: Epel reports she is co-author of the book The Telomere Effect with Elizabeth Blackburn, PhD.