Want to Lower Your Biological Age? Androgen Levels Offer a Clue

With Bu Yeap, PhD, and Stanley Korenman, MD

In men over the age of 70 years young, having a higher level of the primary male sex hormone, testosterone, and the female-predominate sex hormone, estradiol, are linked with a lower biological age.1 The role these androgens may play in the aging process was the focus of a presentation at ENDO 2019, the 101st Annual Meeting of the Endocrine Society, in New Orleans, Louisiana.

Consider that four in five people are aging poorly, meaning they have a lower biological age, brought on by high cholesterol, high blood pressure, and other clinical factors that contribute to poorer heart health.2  And, we can’t change our chronological age, set at birth, but we just may have more control over our biological age, than previously thought.3

It may be possible to slow bioloigcal age by adjusting androgens, male sex hormones.Researchers offer new insights into the possible effect that androgens—male sex hormones—have on their rate of biological aging. Photo: 123rf

What About Biological Age Even Matters?!

Being at a lower biological age means much more than looking younger, it is also likely to indicate that you are healthier because you are aging more slowly. And, the ability to age better the older one gets is a desirable and important goal for most everyone. Best of all, by achieving an optimum biological age, you’re more likely to avoid or at least postpone development of common chronic diseases such as diabetes and heart disease appears more possible.

These clues come from work investigating the role of androgens,3 says the study lead author Bu Yeap, PhD, FRACP, professor of medicine at the University of Western Australia Medical School in Perth. “We set out to answer the question: Do sex hormones modify the process of biological aging? And from the results of our study, it seems that the level of sex hormones do indeed play a key role in the pace that men age.”  

As the life expectancy of the population in this country increases, figuring out how to help people age in a healthier way is crucial, Dr. Yeap tells EndocrineWeb. In conducting this study, Dr. Yeap and his research team report an unexpected discovery— the higher the blood level of the hormone estradiol (a form of estrogen), which is typically higher in women and minimal in men— the lower the biological age of these men.1,3

While this is a great first step, and the results are very encouraging,3 more research is needed. Dr. Yeap says there’s more research to do before we can be fully certain that adjusting the levels of sex hormones‑thereby changing the body’s exposure to different levels of testosterone and estradiol—might actually produce a favorable effect on the pace of biological age.

Telomers Shed More Light On the Process of Biological Aging

Dr. Yeap's method of measuring biological age was to evaluate the length of telomeres,3 which represents an exciting area of research. Telomeres are caps located at the end of each chromosome—akin to the plastic tips of shoelaces, which prevent the shoelace from unraveling. The job of these telomeres is to protect the DNA from getting damaged. When the telomere cap gets clipped, cell division doesn’t work as efficiently, causes the chromosomes to shorten.  

Since the discovery of telomeres, there has been a flurry of attention regarding the function of telomeres in aging and their role in the cancer.3

What we know, at present, is that as telomeres get clipped, it leads to a shortening of the chromosomes as you age; the result is that cells do not function as efficiently, leading to a rise in diseases. Experts know that lifestyle factors including stress, cigarette smoking, obesity, poor diet, and lack of physical activity have each been linked to a shortening of telomeres, accelerating the rate of aging.3  

Until the findings of Dr. Yeap's study offered some insights, the effect of male sex hormones on telomere length has remained a mystery, he says.

Dr. Yeap and his research team set out to examine data collected from nearly 3,000 men, who ranged in age from 70 to 84 years.1 They were not in long-term care facilities but lived in the community. About a third had cardiovascular disease; 14% had diabetes. Their average body mass index (BMI) was 26.5 kg/m2, which is considered slightly above a healthy weight (ie,  BMI of 25.0 to 29.9 kg/m2  indicates a person is overweight).

The research team measured the telomeres in the DNA from the men's white blood cell samples. They also measured sex hormone levels in the men's blood samples.

The investigators evaluated blood samples for levels of androgens: testosterone, dihydrotestosterone, estradiol, and sex-hormone-binding-globulin (SHBG) to look at possible links between these hormones and telomere length.

When they adjusted for factors such as age and cardiovascular disease, they found that estradiol was linked with telomere length. The higher the estradiol, the longer the telomeres, and thus the lower the biological age.

"Having a higher estradiol level was comparable to being 2.4 years younger, or having a body mass index (BMI) that is 3.6 units lower," Dr. Yeap says.   From this study, Dr. Yeap found an inverse association between the SHBG and telomere length—the lower the SHBG, the longer the telomeres.

"Estradiol may preserve telomeres by increasing the activity of an enzyme called telomerase, that lengthens telomeres," Dr. Yeap says. He stresses that his study found an association, not cause and effect, and that much more study is required.

For Now—Focus on a Healthy Lifestyle to Assure Graceful Aging

"These study findings are very preliminary," says Stanley Korenman, MD, Distinguished Professor of Medicine in Endocrinology at the David Geffen School of Medicine, UCLA, commenting on the findings for EndocrineWeb.

"The term biological aging is vague," he says, and the Australian researchers only looked at one measure--the length of telomeres—to find an association between long-term health and the role of sex hormones in men.

People definitely age at different rates, he says. And while some say that lowering biological age holds the promise of keeping chronic diseases at bay, Dr. Korenman points out that most of the time people's health declines because they have heart disease or serious orthopedic issues, for example, not because their so-called biological age suggests they are less healthy.

He adds that while women lose ovarian function more quickly during menopause, they typically still live longer then do men, so there's more to the story than just hormone levels. As for telomeres, men typically have shorter telomere length than women at around the same age, which raises the possibility that exposure to sex hormones may contribute to the length of these structures.

In the lab, researchers have found that exposing telomeres to androgens led to increased activity but in human studies, the findings have been less clear.

"The researchers'  introduce an interesting correlation but it isn’t enough to show a definite cause and effect between androgen levels and biological age," Dr. Korenman says. And the findings that the lower the levels of circulating SHBG are, the longer the telomeres, seems contradictory.

"I would have expected that the higher the estradiol, the higher [also] the SHBG, and the longer the telomeres,” he says, “and that the men with higher estradiol would have higher SHBG because the main stimulus [for it] is estrogen. Yet, they are showing an inverse association between SHBG and telomere lengths."

What Might Biological Aging Mean for Women?

"Our study examined the association of lower estradiol with shorter telomeres in older men," says Dr. Yeap, "therefore, we cannot be certain that the same relationship exists in women."

"However there are experimental studies showing potential mechanisms by which estradiol might influence telomere length, and these mechanisms probably operate in both men and women," he tells EndocrineWeb. "It would be very interesting to perform a similar study in postmenopausal women since they have very low estradiol concentrations, and if this is related to biological aging then the question arises as to when menopausal hormone therapy should be considered."

More Research Needed on Factors Influencing Biological Aging

"The question is whether introducing treatment to change the level s of sex hormones will have an effect on biological aging," Dr. Yeap says. That possibility, as exciting as it sounds, still remains to be seen, he adds.

Yet, in an earlier study,4 his team looked at a group of younger men, on average age 59 years. "We also saw the association between androgen levels and biological age, and we think it's a robust finding," says Dr. Yeap, referring to estradiol levels and longer telomere length.  

What is needed now, he says, is a study in which men are given testosterone and then assessed to see how much of this hormone is converted to estradiol and to look for any changes in telomere length that might result. Dr. Yeap adds: there’s another caveat: these studies have included men only, and mainly Caucasians, so the results can't be generalized widely, only to a similar population as that studied.

Meanwhile? "Stay healthy," he says. Do all the right things: Keep fit by staying active, he says, with a workout that includes resistance exercise, eat wisely, and do whatever you can to remain at a healthy weight.  "That way you are keeping your testosterone levels in a healthy range." And, you are helping to lessen your biological age, even as your chronological age continues to add up.

Neither Dr. Yeap nor Dr. Korenman has any financial disclosures related to this work.

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