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Estradiol level influences telomere length in older men
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NEW ORLEANS — Older men with a higher estradiol level were more likely to have longer telomeres associated with so-called biological age, independent of lifestyle factors and comorbidities, according to findings presented at the Endocrine Society annual meeting.
“In an observational study of 2,913 community-dwelling older men, men who had higher levels of estradiol had longer telomeres, a measure of younger biological age,” Bu Beng Yeap, MBBS, FRACP, PhD, a professor at the University of Western Australia Medical School and endocrinologist at Fiona Stanley Hospital in Perth, Western Australia, told Endocrine Today. “These findings suggest that sex hormones might influence biological aging in men. A randomized controlled trial would be needed to test what the effects of treatment with testosterone, which is converted to estradiol, are on telomere length in men.”
The attrition of telomeres, which protect the physical ends of chromosomes from fusion and degradation, results in cellular senescence, Yeap said. Leucocyte telomere length reflects the length of telomeres in various tissues, and shorter leucocyte telomere length is a marker of advancing biological age.
In past studies, researchers have found associations between bioactive metabolites of testosterone, dihydrotestosterone and estradiol with leucocyte telomere length in a population of predominantly middle-aged men; however, the relationship between the hormone levels and biological age was unclear, Yeap said.
“The question we wanted to ask was, do sex hormones modify the process of biological aging, and is that why there may be a link between low sex hormone levels and increasing comorbidities in older men?” Yeap said during a press conference. “There is some experimental evidence, from cells and from mice, that perhaps estradiol actually regulates telomere length in experimental settings. We wanted to test this in men.”
Yeap and colleagues analyzed data from 2,913 men aged 70 to 89 years who were not living in long-term care facilities (mean age, 77 years). The men provided early-morning blood samples to assess testosterone, dihydrotestosterone and estradiol using mass spectrometry and sex hormone-binding globulin using immunoassay. Researchers measured leucocyte telomere length using a multiplex quantitative polymerase chain reaction method, with findings expressed as the amount of telomeric DNA relative to beta-globin, a single copy control gene (ie, the T/S ratio).
Within the cohort, the average difference per decade of age was –0.46 nmol/L for testosterone, –0.11 nmol/L for dihydrotestosterone, –7.5 pmol/L for estradiol, +10.2 nmol/L for SHBG and –0.065 for T/S ratio.
The researchers found that testosterone and dihydrotestosterone levels in the men were not associated with leucocyte telomere length in multivariate analyses; however, estradiol level was positively correlated with T/S ratio (P = .039), with results persisting after excluding highest and lowest 1% of values (P = .037).
SHBG was inversely correlated with T/S ratio (P = .004). In analyses adjusted for age, BMI, cardiovascular disease, diabetes status, alcohol intake, smoking status, physical activity, lipid levels and hypertension status, estradiol remained associated with T/S ratio (P = .043), Yeap said. In a model that combined estradiol and SHBG, researchers found that estradiol remained positively associated with T/S ratio (P = .014) and SHBG remained inversely associated (P = .037).
“The magnitude of increase in T/S ratio associated with a 1 [standard deviation] higher plasma [estradiol] concentration was comparable with having a BMI 3.6 kg/m² lower,” according to the abstract.
Yeap said the causality cannot be inferred from an observational, cross-sectional study, adding that additional research is needed to determine whether sex hormone exposure modulates male biological aging. – by Regina Schaffer
Reference:
Yeap BB, et al. OR18-2. Presented at: The Endocrine Society Annual Meeting; March 23-26, 2019; New Orleans.
Disclosure: Yeap reports no relevant financial disclosures.
Perspective
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Elissa Epel, PhD
Sex hormones hold important clues to understanding biological aging, but there are no simple answers or treatments. We know from basic research that estrogen can upregulate telomerase. Estrogen increases telomerase in experimental basic studies, and women have longer telomeres, starting from birth. Sex hormones and telomere length have not been systematically studied in humans, but this is an area ripe for translational discoveries.
This new study by Yeap and colleagues is an important clue in this complex puzzle linking sex, sex hormones, cell aging and longevity. In a large sample of older men, with a highly accurate assay, they found that higher levels of estradiol, a metabolite of testosterone, were associated with longer telomeres. This is a small effect but a signal that in older men, higher levels of estradiol may be beneficial.
The new study underscores the exciting potential of examining supplementation effects in healthy, older men to increase telomere stability and slow immune cell aging, ultimately with the hope it would increase health span. The implications of this study, like many other cross-sectional studies on hormone levels, are not clear — it is certainly not the case that we can just supplement hormones and expect anti-aging effects. The literature on estrogen and men’s health finds both low levels and high levels are associated with health risks, but this area is low-hanging fruit for more high-quality experiments and clinical trials.
How can you protect your telomeres? This study points to a great opportunity for scientists to learn useful discoveries on how sex hormones may promote healthy telomeres. In addition to directly manipulating hormone levels, which has risks, there is a lot people can do now to slow the rate of cell aging. Small daily behaviors add up over years, including increased physical activity, good-quality sleep, stress management and a whole-food diet, to maintain more stable telomeres and lower inflammation, protecting from early disease. Plan your day accordingly.
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