Obesity Archives | Misha Blagosklonny

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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Dr. Marina Antoch of Roswell Park Comprehensive Cancer Center discusses her 2017 study published by Aging entitled, “Physiological frailty index (PFI): quantitative in-life estimate of individual biological age in mice.”

Researchers explain their studies that were published in Aging

My name is Marina Antoch, and I am a member of Department of Pharmacology and Therapeutics for Roswell Park Cancer Institute. And actually working here at Roswell for 10 years now. Recently my group, in collaboration with few other laboratories and the local biotech startup company, Everon Biosciences, summarize the recent research in the paper that was published in the journal, Aging. This paper is related to working out a novel approach that will allow us to assess the overall health in the preclinical animal model organelle.

Working with the company that’s really interested in developing some therapeutics that could combat aging, slow down the aging, we really need to get some quantitative tools that we can use to assess the efficacy of those molecules of those potential drugs that they identify in their preclinical studies. There were few works that would suggest some approaches how we can do that, but none of these really satisfy the goals that we have.

So we have to think of some other approaches that we may use, and there were several requirements that we really need for developing the successful protocols. First of all, we wanted this protocol to be absolutely non-invasive for our preclinical animal models, so it could be repeated on the same subject for several times. We can actually look through the lifespan of the subject, how these parameters and overall health is changed with age. They have to be really quantitative. So we didn’t really want to rely on some observational things like the hair grain, for example, that’s been considered the hallmark of aging for many years. Many of these observations, they really require coring by several individual observers and then they are compared, and they’re very subjective. (We) really wanted to get something more objective that we could put in numbers.

This manuscript that was published actually summarized almost three-year work that was dedicated to this problem. We tried many different approaches and finally came up with a protocol that we called determining physiological frailty index. And this frailty index is just the cumulative estimate of many, many physiological parameters that are related to the health of the animal. And they’re very relevant to human studies since these such parameters as body weight or physical strength that we could measure, usually using special equipment or blood pressure that we can measure in animal models-very similar to how we do it in humans, blood cell parameters, and a few others that can really give us the quantitative assessment of each parameter. Then we compare how much it is in older animals – or in animals that don’t feel well. How much of these parameters differ from when compared to the younger animals, and that gave us a certain quantitative estimate. So why is that important? It’s important for the reason of testing, as I mentioned already, various potential biologicals that would be developed as anti-aging drugs.

**Figure 1.** **Assessment of individual biological age of NIH Swiss mice**.

This protocol will now allow us to assess, quantitatively, the health status of animals then treat them with potential therapeutics, and then down the road, repeat this measurement to see if this frailty index, brought any improvement or not, and that would be indicative of the efficacy of the therapy. So this is one of the major goals of our research and why we developed this protocol. But for all future studies, we have actually another thought in mind, how we may use this particular approach. We’re now related to cancer research as you may know, due to the really successful development of many anti-cancer drugs, and many anti-cancer therapies. There are more and more cancer survivors. Actually in 2016, the American Cancer Society published statistics saying that there’s about 15 million people that went through the very harsh chemotherapeutic and radiation therapies. They are cancer-free. They never had relapsed cancer, but these therapies definitely affect a lot of other aspects of their health. And one of those aspects, besides any specific diseases, that they may develop is the accelerated aging.

With the development of more and more therapeutics, the expectation is that in 2026, there’ll be more than 20 million of cancer survivors. We’ll really need to be thinking about developing novel cancer therapeutics. We really should think not to make them more efficient and less toxic, but also to be able to diminish their damaging effect down the road at the latest stages of the life of basically to improve the quality of life of cancer survivors by adjusting the treatments at the time that we treat cancer. So we have less problems later on. To do that first, we have to test this in our preclinical models and for success of those tests, we really needed some quantitative assay that we can apply.

We think that our protocol of physiological frailty index would serve this purpose very well. So, basically, testing the efficacy and the therapeutic efficacy of different chemotherapeutic drugs. We may also look on a long-term effects to see how that affects animals health and adjust treatments based on the preclinical evaluation. This is why we think it’s really an important tool that could be very useful in many aspects of preclinical studies, and maybe sometimes applied then as many of preclinical studies translated into the clinical applications.

I’m also thinking that it may be very relevant for treatment of childhood cancers. Childhood cancers are very specific type of cancers. First of all, the regiments are actually the same as are worked out for adult people. Although young people and adult people are very different physiologically. They’re just adjusted by the weight, the age a little bit. But in principle, they are about the same.

The rate of cure for some types of childhood cancers nowadays is also pretty sufficient. So there is a large population of kids that went through chemotherapy and radiation that was applied to a very critical moment in their development. So they are effective. It’s really very significant. Actually the longevity of those childhood cancer survivors is statistically lower and they will premature age and develop a lot of different complications. So I think that that could be particularly important for treating various types of childhood cancers, and that can really affect the way we are treating childhood malignancies.

If we are able to reach our goal and adjust the treatment so we’re focusing not only on immediate therapeutic effect, but take into account these long-term complications that would inevitably arise after the treatment, we can significantly improve the quality of life of cancer survivors. That would be a very significant impact on the overall health of the population, I would say.

Click here to read the full study 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.

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

Tag: Obesity

Behind the Study: Interview with Dr. Marina P. Antoch

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