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BMI Correlates With Accelerated Epigenetic Aging in Young Adults

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In a recent study, researchers from the University of Alabama at Birmingham’s Department of Pediatrics examined the relationship between measures of obesity and DNA methylation in young adults.

BMI Correlates With Accelerated Epigenetic Aging in Young Adults

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While the study of genetics focuses on heredity and alterations in the genetic code itself, epigenetics refers to the changes in gene expression that occur as a result of environmental or lifestyle factors. Advances in epigenetic research have allowed measures of DNA methylation (DNAm) (epigenetic clocks) to illustrate clear links between obesity, accelerated epigenetic aging and a variety of negative health outcomes in older adults. Despite these advances, there is a lack of research about these correlations and sex-based variations among young adults. The ability to detect accelerated epigenetic aging in young adulthood could potentially be used to prevent the onset of chronic diseases and improve health outcomes later in life.

“Moreover, few studies have included replication across measures of obesity and epigenetic aging to examine the robustness or specificity of these effects. Finally, little is known about sex differences in the links between obesity and epigenetic aging, despite evidence of substantial sex dimorphism in both physiological and epigenetic aging [20].”

In a recent study, researchers Christy Anne Foster, Malcolm Barker-Kamps, Marlon Goering, Amit Patki, Hemant K. Tiwari, and Sylvie Mrug from the University of Alabama at Birmingham’s Department of Pediatrics examined the relationship between obesity and measures of DNAm in young adults. They also investigated whether there is a sex-dependant correlation between obesity and DNAm in young adults. On January 18, 2023, their research paper was published in Aging’s Volume 15, Issue 2, and entitled, “Epigenetic age acceleration correlates with BMI in young adults.”

Research and Results

Here, the researchers explored the relationship between measures of obesity and epigenetic age acceleration in young adults. The team included a cross-sectional community sample of 290 healthy young adults—with 60% being female, 80% African American, 18% White, and a total mean age of 27 years old. The researchers measured participant BMI and waist circumference, and also calculated their epigenetic age acceleration using four epigenetic age estimators (derived from salivary DNA): Hannum DNAm, Horvath DNAm, Phenoage DNAm, and GrimAge DNAm. In addition, they collected data on covariates, including age, sex, race, parental education, and income-to-needs ratio.

After covariates were adjusted for, the researchers found that DNAm PhenoAge was higher in participants who had higher body mass index (BMI) and waist circumference in both sexes, with a stronger effect on BMI in males compared to females. Horvath DNA methylation age was associated with participants who had larger waist circumferences, but not BMI. Higher Hannum DNAm age was associated with both higher BMI and waist circumference in men, but not in women. In this study, GrimAge was not associated with either BMI or waist circumference. As a whole, none of the associations with the DNAm indicators varied by race. The researchers found that scoring higher on one or more of the four DNAm indicators was associated with an older chronological age, lower socioeconomic status, being female and White, as well as saliva cell composition. 

“Together, these results suggest that higher BMI and waist circumference are associated with higher epigenetic age in young adulthood. Because the analyses adjusted for chronological age, associations with higher epigenetic age indicate faster epigenetic aging [22]. Importantly, this study demonstrated associations between obesity and epigenetic aging using DNA from saliva, which involves a non-invasive sample collection compared to other tissues (e.g., blood) and thus can be more readily translated into clinical practice, highlighting the usefulness in young adults.”

Significance and Limitations

These findings are significant because they suggest that body weight plays a role in determining epigenetic age acceleration, which in turn can affect overall health and lifespan. Previous research has shown that epigenetic age acceleration is associated with increased risk for age-related diseases such as cardiovascular disease, type 2 diabetes and certain cancers. However, it is important to note that this study only shows a correlation between BMI and epigenetic age acceleration and does not provide evidence of causality. It is possible that other factors, such as diet, exercise and stress levels, could also contribute to the relationship between BMI and epigenetic age acceleration.

The authors were forthcoming about several study limitations in their research paper, including a relatively small sample size which limited statistical power and precluded rigorous analysis of individual CpG sites. The original sample was locally representative but experienced some differential attrition over time, which could limit generalizability to certain populations. Epigenetic clocks have been tested primarily in White populations and may be less relevant to African American individuals who comprised the majority of this sample. This study used salivary DNA, so replication using DNA extracted from other tissues will be important for future work. The cross-sectional design did not allow testing directional effects between BMI and epigenetic aging over time. None of the CpGs used in calculating methylation age were part of known causal effect on BMI as per Mendelian Randomization studies; further modeling with outcomes from other tissues impacted by obesity may provide more insight into methylation aging process.

Conclusions

In conclusion, this study sheds light on the relationship between BMI and epigenetic age acceleration in young adults. The results suggest that young adults with higher BMIs may be aging faster and at a higher risk for age-related diseases. These findings highlight the importance of maintaining a healthy weight and lifestyle, not only for weight management but also for overall health and lifespan.

In the context of the growing obesity epidemic and the increasing focus on personalized medicine and preventive health, this study provides valuable insights into the potential health impacts of body weight and the role of epigenetics in health and disease. Further research is needed to fully understand the mechanisms behind this relationship and to determine the best approaches for improving health and lifespan in young adults.

“In conclusion, this study extends prior research by demonstrating the association between obesity and salivary epigenetic aging in young adult males and females. These findings are of interest to those who are interested in epigenetic age acceleration as a potential biomarker. They also support future research examining obesity as a causal risk factor for epigenetic age acceleration. The findings underscore the importance of testing sex differences and including multiple epigenetic clocks in future research. Overall, the present results add to mounting evidence that obesity affects cellular aging across multiple tissues early in the lifespan.”

Click here to read the full research paper published by Aging.

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Aging is an open-access, peer-reviewed journal that has published high-impact research papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

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Trending With Impact: Can Job Stress Cause Epigenetic Aging?

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The association between job-related stress and epigenetic aging was investigated using five epigenetic clocks and a Finnish cohort.

Job stress

The Trending With Impact series highlights Aging (Aging-US) publications that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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In aging research, recent evidence has encouraged more focus on investigating socioeconomic status (SES) and its role in human health trajectories. Previous studies have used DNA methylation measures and epigenetic clocks to demonstrate a consistent association between low SES and epigenetic age acceleration (EAA). Moreover, researchers have identified a need to further investigate the relationship between SES characteristics and aging.  

“Little is known whether current occupational characteristics or job-related stress – crucial SES characteristics – are associated with EAA.”

Recently, researchers—from Imperial College London, University of Sassari, University of Eastern Finland, Karolinska Institutet, University of Oulu, and the Italian Institute for Genomic Medicine—conducted a research study in an effort to help elucidate potential mechanisms by which work characteristics and job stressors may be impacting health and accelerating aging. Their trending research paper was published by Aging (Aging-US) on February 2, 2022, and entitled, “Work-related stress and well-being in association with epigenetic age acceleration: A Northern Finland Birth Cohort 1966 Study.” 

The Study

The researchers in this study included 604 participants from the Northern Finland Birth Cohort 1966. Participants in this cohort were all born in the provinces of Oulu and Lapland, Finland, in 1966. DNA samples were collected and used to determine the relationship between biomarkers of aging, job stress and common environmental factors associated with age acceleration, including obesity, smoking, alcoholism, education status, and physical activity. The team used five different epigenetic clocks as biomarkers of aging: HorvathAA, HannumAA, PhenoAgeAA, GrimAgeAA, and DunedinPoAm.

“In this work, we assessed the association (and its magnitude) of five biomarkers of epigenetic age acceleration with work-related stress and well-being indicators (as well as other employment characteristics) in the Northern Finland Birth Cohort 1966, at 46 years old.”

Participants also filled out a clinical examination questionnaire, a modified Karasek’s Job Content Questionnaire (to assess job strain) and the Occupational Stress Questionnaire (to measure effort-reward imbalance). A number of descriptive statistics were collected from each participant, including body mass index (BMI); educational level; alcohol consumption; smoking habits; physical/leisure activity; job status (employed/unemployed); employer type (private or state/municipality); occupational group (white-collar or blue-collar); and job exposure. The researchers defined “job exposure” as job strain, effort-reward imbalance, overcommitment, occupational physical activity, work-favoring attitude, job security and work engagement, history, hours, and shift. 

The Results

After using linear regression models to analyze the adjusted and unadjusted pooled data (males and females together), the researchers found that job strain was not significantly associated with EAA using any of the epigenetic clocks. All five clocks associated smoking and obesity with accelerated aging (at varying significance). However, alcohol use (even heavy use) was not significantly associated with accelerated aging on any of the clocks. PhenoAgeAA associated job strain, active work and white-collar work (compared to blue-collar) with decreased aging. According to the Hannum and HorvathAA biomarkers of aging, people who worked more than 40 hours per week showed increased EAA.

“Once we stratified analyses by sex, a different pattern of association emerged, with women leading on the statistically significant results.”

Next, the researchers further stratified the results by sex. In men, high-intensity physical effort at work had a decreased aging effect. However, for women, high-intensity physical effort at work had an increased aging effect. The researchers point out that these clocks may have contradictory result due to the fact that women and men often present with diverse, sex-specific epigenetic patterns. While a direct correlation between job stress and epigenetic aging have yet to be proven, the degree of association between work characteristics and biomarkers of epigenetic aging in this study did vary by sex.

Conclusion

“This paper is one of the first attempts to address the working dimension of epigenetic age acceleration indicators, to the best of our knowledge.”

The Northern Finland Birth Cohort 1966 is a useful sample for studying a general population, and many confounders were removed in doing so. However, the researchers were forthcoming about some limitations that remained in this study. The unique characteristics of the cohort, as well as the questionnaires, may be responsible for the results seen in the study. The researchers suggest that additional studies be carried out in other societies and on different types of jobs to account for gender differences. 

“Our results suggest that women and men present different associations with different epigenetic distributions regarding work-related stress indicators.”

Click here to read the full research paper published by Aging (Aging-US).

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Aging (Aging-US) is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

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The Epigenetic Clock, Aging, and Rejuvenation

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Researchers discuss the role that the epigenetic clock may play in the aging process and in rejuvenation as an approach to set back epigenetic age.

Figure 3. Morphological changes induced by long-term OSKM gene action in human umbilical cord perivascular cells (HUCPVC).
Figure 3. Morphological changes induced by long-term OSKM gene action in human umbilical cord perivascular cells (HUCPVC).

The Top-Performer series highlights papers published by Aging that have generated a high Altmetric attention score. Altmetric scores, located at the top-left of trending Aging papers, provide an at-a-glance indication of the volume and type of online attention the research has received.

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A centenarian is a human that has lived as long or longer than one hundred years. These individuals are marvels to aging researchers and have been studied at length in hopes of uncovering clues about the mechanisms that drive aging. Many researchers have crafted views and theories about the roots of gerontology; these curiosities have preceded the development of modern science.

In an effort to describe different views and theories of aging—leading to the emergent view of the epigenome as the driver of aging—researchers from the National University of La Plata, National University of Cordoba, World Academy of Art and Science, and Betterhumans Inc., authored a research perspective published by Aging in 2021. This well-written paper describes the role that the epigenetic clock may play in both the aging process and in rejuvenation as an approach to set back epigenetic age. The paper was entitled, “Aging and rejuvenation – a modular epigenome model.”

“The hypothesis proposing the epigenome as the driver of aging was significantly strengthened by the converging discovery that DNA methylation at specific CpG sites could be used as a highly accurate biomarker of age defined by the Horvath clock [5].”

THE EPIGENETIC CLOCK

Throughout our lifetime, the rate of change in DNA methylation at age-dependent CpG sites has been found to consistently correlate with our rate of epigenetic aging and organismal aging. In 2013, researcher Stephen Horvath devised a mathematical algorithm using DNA methylation at specific CpG sites that is a highly accurate biomarker of age. 

“In humans, the epigenetic age calculated by the clock algorithm shows a correlation of 0.96 to chronological age and an error margin of 3.6 years, an unprecedented accuracy for a biomarker of age [5, 24].”

In human babies, from birth to one year old, researchers explain that the ticking rate of the epigenetic clock is very high, as is our rate of aging at this point in the lifecycle. Then, from one to 20 years of age, the rate progressively decelerates. After age 20, the ticking rate is much slower. Among individuals with conditions such as cancer, HIV, obesity, Alzheimer’s disease, and even alcohol abuse, the ticking of the epigenetic clock and aging rate is, unsurprisingly, much higher. In another example, the rate of epigenetic aging is slower in supercentenarians and their children compared with non-centenarians. 

“There is compelling evidence that the ticking rate of the clock is significantly correlated with the rate of biological aging in health and disease.”

THE EPIGENETIC CLOCK & AGE REJUVENATION

Even while they continue to proliferate, embryonic cells (ES) may remain indefinitely young—in a type of “suspended animation.” The epigenetic clock does not tick in embryonic cells, until they differentiate.

“In ES cells, the epigenetic clock does not tick [5] nor does the circadian clock oscillate [26]. Only when ES cells differentiate, both clocks become active and cells begin to age.” 

Over the years, there have been clues indicating that it is possible to rejuvenate non-reproductive (somatic) cells back to induced pluripotent stem (iPS) cells, or embryonic-like cells. When somatic cells are reprogrammed to iPS cells, their epigenetic clocks stop ticking, their circadian clocks cease to oscillate, and ultimately, their epigenetic clock is set back to zero (or close to zero). These clues came from the development of animal cloning in the early 60s and, more recently, cell reprogramming.

The authors of this research perspective explain rejuvenation strategies including cell reprogramming, cyclic partial cell reprogramming, and other non-reprogramming strategies.

Two cell rejuvenation studies were described by the authors of this paper which suggest that, even at advanced stages of age, the epigenome continues to be responsive to command signals, including the OSKM genes, also known as the Yamanaka factors. This finding is compatible with the hypothesis that aging is not associated with DNA damage. The researchers explain two additional possible theories: 1.) Aging is preprogrammed in our DNA and due to progressive epigenome disorganization and loss of epigenetic information. 2.) Aging is not a programmed process, but a continuation of developmental growth driven by genetic pathways, such as mTOR.

“What seems to be clear is that epigenetic rejuvenation by cyclic partial reprogramming or alternative non-reprogramming strategies holds the key to both, understanding the mechanism by which the epigenome drives the aging process and arresting or even reversing organismal aging.”

CONCLUSIONS

In summary, the researchers explain that what the few initial study results seem to suggest is that when the epigenetic clock is forced to tick backwards in vivo, it is only able to drag the phenotype to a partially rejuvenated condition. However, the researchers emphasize that no firm conclusions should be drawn from the very few experimental results currently documented.

“Since we now have molecular tools, like the Yamanaka factors, that allow us to make the clock tick backwards, the time is ripe for opening a new dimension in gerontology, moving from aging research to epigenetic rejuvenation research.”

Click here to read the full research perspective, published by Aging.

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Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

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Trending with Impact: Epigenetic Age Decreased in Diet & Lifestyle Study

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Researchers conducted an eight-week study on diet and lifestyle among a small cohort of 43 male participants between the ages of 50 and 72.

Happy senior couple buying fresh food at the market

The Trending with Impact series highlights Aging publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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In addition to the well-known personal and social costs of aging, the economic costs of aging are also considerably high. Research finds that investing in delaying aging is much more cost-effective than disease-specific spending. A study found that if Americans as a whole delayed their aging by 2.2 years (while extending healthspan), economic savings over 50 years could amount to a cumulative $7 trillion.

“The growing health-related economic and social challenges of our rapidly aging population are well recognized and affect individuals, their families, health systems and economies.”

Across three countries (the United States, Canada, and Israel), researchers from the Institute for Functional Medicine, American Nutrition Association, National University of Natural Medicine, Ariel University, McGill University, and the University of California, conducted a new pilot study on the effects that diet and lifestyle intervention have on aging among healthy males between the ages of 50 and 72. This research paper was published in Aging’s Volume 13, Issue 7, and entitled, “Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial.”

The Study

The researchers organized a cohort of 43 healthy adult males between the ages of 50 and 72. Half of the participants (n=21) completed an eight-week treatment program, and the other half (control group=22) received no intervention. Interventions within the treatment program included regimented diet, sleep, exercise, relaxation guidance, and supplemental probiotics and phytonutrients. Prior to the treatment program, participants were enrolled in a preliminary education week to become acquainted with the researchers’ prescribed dietary and lifestyle interventions.

“To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males.”

Diet Prescription

Researchers prescribed the participants with mostly (not entirely) plant-based diet instructions to consume measured portions of liver, eggs, dark leafy greens, cruciferous vegetables, colorful vegetables (excluding white potatoes and sweetcorn), beets, pumpkin seeds (or pumpkin seed butter), sunflower seeds (or sunflower seed butter), methylation adaptogens, berries, rosemary, turmeric, garlic, green tea, oolong tea, animal protein, and low glycemic fruit. They were prescribed two daily doses of PhytoGanix®, which is a combination of organic vegetables, fruits, seeds, herbs, plant enzymes, prebiotics, and probiotics. A daily two-capsule dose of UltraFlora® Intensive Care, containing Lactobacillus plantarum, was also prescribed.

General guidance included that participants should choose organic food products over conventional, and to consume “healthy” oils and balanced types of fat, including coconut, olive, flaxseed, and pumpkin seed oil. Participants were told to avoid consuming added sugar, candy, dairy, grains, legumes/beans, and to minimize using plastic food containers. In addition, the prescription instructed participants to stay hydrated and not to eat between 7pm and 7am.

Lifestyle Prescription

The participant exercise prescription was a minimum of 30 minutes per day for at least five days per week, at 60-80% intensity. They completed two 20 minute breathing exercises daily, using the Steps to Elicit the Relaxation Response process developed by Herbert Benson, MD. Participants were prescribed to sleep a minimum of seven hours per night.

Measuring Epigenetic Age 

“Currently, the best biochemical markers of an individual’s age are all based on patterns of methylation [5].”

To extract DNA from the participants, researchers collected saliva samples and evaluated their RNA and DNA. They used methylation kits, assays, and the Horvath DNAmAge clock to conduct genome-wide DNA methylation analysis and calculate epigenetic age (DNAmAge) at the beginning of the study, and at the end.

“Horvath’s DNAmAge clock predicts all-cause mortality and multiple morbidities better than chronological age. Methylation clocks (including DNAmAge) are based on systematic methylation changes with age.”

Conclusion

According to the Horvath DNAmAge clock, participants in the treatment group scored an average 3.23 years younger at the end of the eight-week program when compared to participants in the control group. While these findings are meaningful, additional studies with a larger cohort size, longer duration, and other human populations will be needed in order to confirm these results.

“Notably, the shorter timeframe of this study and the scale of potential reduction, while modest in magnitude, may correlate with meaningful socioeconomic benefits, and appears to have the potential to be broadly achievable.”

Click here to read the full study, published on Aging-US.com.

Click the links below for more information on corresponding author, Dr. Kara Fitzgerald:
Biological Aging Summary | Instagram | Facebook | Twitter | General Site | Younger You Program

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Aging is an open-access journal that publishes research papers monthly in all fields of aging research and other topics. These papers are available to read at no cost to readers on Aging-us.com. Open-access journals offer information that has the potential to benefit our societies from the inside out and may be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact media@impactjournals.com.

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