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Beyond Birthdays: Decoding Biological Age with Epigenetics and Innovative Testing

Biological Age Biological Age
Longevity By Nature
 
EuroMedica

Last year I looked up the phrase “biological age” one time, that’s all it took and from then on I was inundated with ads, seemingly at every website I visit, extolling the endless benefits of the “most advanced” biological age tests and accompanying supplements that all promise to “turn back the hands of time” and “extend not only your lifespan but also dramatically improve you healthspan.” So here I am, fairly educated in the area of functional medicine and all of this information, the marketing copy and ads got so overwhelming for me it was difficult to decipher what is real and what isn’t. If I’ve found myself in this boat, I’m guessing others have too (or maybe I’m a lone ranger and am just grossly behind the curve and have to pay closer attention). With all of that said, obviously I’m not an expert in the area of biological age testing, however, over the past year I’ve dug in as much as I could, spoken to industry leaders and gotten a decent sense of the landscape. And there are definitely some areas to pay attention to that are incredibly exciting and areas to understand for when patients start asking about these types of tests and their validity.

What I’ve done here is compile some key information related to biological age, the tests that are out there, some of the natural compounds that might actually make a difference (and others that may not) and how this might be useful in clinical practice—whether you make the move to implement these types of tests in practice or simply choose to provide patients some guidance when they ask about them—which is inevitable.

Biological Age 101

First things first, what is meant by “biological age?” Your biological age is not just about counting candles; it’s about understanding the inner workings of your body’s clock. This is where epigenetics come into play; epigenetics change the gene expression without altering the DNA itself. Amid various epigenetic markers, methylation takes center stage, offering a peek into the internal aging process. Biological age zeroes in on the physiological changes within individuals, creating that diversity you see between two people who share a birthday. Ever wondered why one person looks a decade younger but shares the same number of candles? It can come down to the magic of methylation, where methyl groups attach and detach, acting as dimmer switches for gene expression. These switches respond to lifestyle factors like sleep, diet and stress, influencing how your cells function. The exciting twist? You can influence methylation and thus slow down and even reverse your biological age by tweaking these factors. While genetics play a role, over half (60 percent) of your gene expression is in your hands. Nutrition, exercise, sleep, stress—they all influence biological age, or you could refer to it as epigenetic age, making it a powerful metric for health and lifespan.

Methylation Based Testing Algorithms

The groundbreaking world of DNA methylation-based biomarkers has recently been unveiled by forward-thinking molecular biologists. As we alluded to, epigenetic age is determined by a sophisticated mathematical algorithm rooted in the methylation state of specific genomic spots, which is redefining how we gauge the passage of time. DNA methylation is the gold standard among age-related biomarkers. Its prowess lies in detecting the acceleration of aging, AKA the “pace of aging,” long before the telltale signs and clinical symptoms emerge.

Embarking on a journey through the timeline of epigenetics and algorithms unveils a fascinating saga. From Fleming’s chromosome discovery in 1879 to the groundbreaking algorithms of Horvath and Hannum in 2011 and 2013, respectively, the evolution of epigenetic clocks mirrors the relentless pursuit of understanding biological age. Fast forward to 2020, and innovative companies like TruDiagnostic are translating these metrics into practical insights for physicians and their patients.

Multi-generational Evolution of Testing

The journey of epigenetic methylation clocks began with the first generation, initially designed to predict the chronological age of individuals. However, as these clocks improved, they gravitated toward predicting the exact chronological age, leaving us questioning the practicality of such precision when most people are well aware of their birthdates. It became evident that what we truly desired was a measurement of the aging process itself—the reason behind individuals in their 70s appearing as youthful as those in their 50s, or vice versa. This pursuit of understanding phenotypic variation and the real essence of aging led to the transition to second-generation clocks in 2017.

The shift to second-generation clocks marked a crucial turning point as they began predicting biological features of aging. This generation delved into more meaningful indicators such as telomere length, time until death, and, in the case of PhenoAge, nine blood-related biomarkers. The focus broadened from a fixation on chronological age to a nuanced examination of how individuals age and the factors influencing their aging process. The positive outcome of this shift was reflected in the clocks’ heightened predictive abilities, particularly in foreseeing outcomes like mortality and disease.

Taking the evolution further, the DunedinPACE measure emerged as a third-generation clock, offering a longitudinal perspective by tracking changes in 19 aging biomarkers over time within a group. While lacking direct methylation measures, this innovative approach succeeded in mitigating confounding factors such as generational exposures.

In a recent PNAS paper comparing various clocks, the evidence strongly supports the use of clocks trained on biological phenotypes, particularly second and third-generation clocks, in consistently associating epigenetic age acceleration with poorer health and mortality.

The Wide World of Various Tests

So, which company offers the tests that have validated, useful information. Before diving into that, it’s worth spending a minute on considering why someone wants to take the test in the first place and understanding what information will be revealed. Most physicians and patients embark on this journey to gauge their aging rates, seeking insights into whether they’re aging gracefully and thus shielded against potential negative outcomes or if they might be on a fast track of accelerated aging and facing heightened health risks.

For those testing with the purpose of understanding their aging trajectory, it becomes crucial to choose an algorithm or clock that has demonstrated a tangible link to aging outcomes. Presently, companies like Elysium, Tally Health, DoNotAge, Mudho and EpiAge use methods that lack published data on the algorithms they use and any correlation with health and disease; they employ the earliest generation of testing. The singular algorithm currently offering validated insights via the third generation of testing is the DunedinPACE algorithm, accessible through SRW, Novos Labs and TruDiagnostic.

Also something to note, the cell type that is used in the test kit. When it comes to extracting DNA for an accurate epigenome scan, blood stands as the sole validated specimen. Although saliva and urine are more convenient to collect, these methods lack the robust scientific validation necessary to support their reliability. Opting for a testing company shouldn’t entail sacrificing results for the sake of easy collection. It’s about finding a balance that ensures both convenience and the scientific rigor needed to obtain accurate and meaningful insights.

Recent Advancements of Bio Age Assessment

We’ve focused heavily on methylation and thus, epigenomics, however, there are other “omics” fields that lend incredible insight into aging. Metabolomics, phenomics, proteomics and transcriptomics all carry insights relative to aging biology. And a multi-omic biobank has been developed in order to pull these vital data and compile them into one test. At present, one company is taking this muli-omic approach, leveraging the clocks trained to phenotype variables, as with DunedinPACE and PhenoAge and combining with the clocks trained to time until death, GrimAge. This test is called OMICm Age Test, which is the best-performing epigenetic clock to date. It is the only epigenetic clock with greater than 90 pecent accuracy of death prediction within 10 years. It also calculates your biological age, your disease risk, your pace of aging, telomere length and your fitness age. It also reflects how your body has responded to other lifestyle choices such as smoking and alcohol consumption.

Harvard’s Nutritional Research in the Field of Aging

A pivotal stride in this area of research involves harnessing artificial intelligence to uncover novel associations between metabolites and proteomics in relation to biological aging. In this exploration, Harvard researchers sought to identify the metabolites, clinical values and proteins that exhibited the highest predictability for longevity. Their investigation unveiled a total of 38 factors with predictive power for time until death, including several nutrition-related biomarkers that served as the blueprint for enhancing epigenetic aging.

The lineup of key nutritional compounds includes calcium alpha-ketoglutarate, uridine monophosphate, ergothioneine, N-acetyl cysteine, lutein (carotene-2,2,-diol), Aronia melanocarpa extract and zinc. Many of these boast extensive publications outlining a myriad of benefits in the context of aging.

This data also helped inform the development of OMICm Age as taken into account that individuals with higher plasma concentrations of uridine and lutein generally exhibited a more favorable OMICm Age, correlating with longer lives and reduced morbidity. Ingredients like zinc and Aronia melanocarpa extract were found to influence other OMICm Age-measured variables, particularly by boosting PON1 (serum paraoxonase and arylesterase 1) activity.

PON1, encoded by the PON1 gene, is a crucial enzyme with anti-atherosclerotic properties and a major component of HDL cholesterol (good cholesterol). Activation of the PON1 gene by PPAR-γ enhances synthesis and release of the paraoxonase 1 enzyme, curbing atherosclerosis. In the OMICm Age cohort, researchers discovered a positive association between higher PON1 activity levels and better aging. Studies have suggested that Aronia melanocarpa extract can elevate PON1 activity levels by more than 15 percent, further emphasizing its potential impact on the aging process.

Summary

Understanding one’s biological age is a journey is a venture into the intricate world of internal clocks and epigenetics. Methylation, a key player, allows us to influence and potentially reverse our biological age by adjusting lifestyle factors. The recent breakthrough of DNA methylation-based biomarkers, encapsulated in sophisticated algorithms, redefines our ability to measure aging. From the pioneering clocks of Horvath and Hannum to the current innovations by companies like TruDiagnostic, the evolution of testing methods mirrors a relentless pursuit of unraveling the mysteries of biological age.

The multi-generational shift in testing approaches signifies a move from simply predicting chronological age to understanding the essence of the aging process itself. Second and third-generation clocks, exemplified by DunedinPACE, delve into more meaningful indicators, providing insights into health outcomes and mortality. The choice of a biological age test becomes pivotal, with an emphasis on selecting algorithms with tangible links to aging outcomes. As we navigate the complexities of aging, the power to influence and understand our biological age lies in the dynamic interplay between genetics, lifestyle and innovative testing methodologies.

Adam Killpartrick is a chiropractor and functional medicine practitioner, CNS and DACBN. He has worked in clinical practice as well as held various positions within the supplement space, most recently as chief science officer and senior leadership team executive of a leading professional brand. He has also lent his expertise to the development of patented innovations and has had his research papers published in Molecules and International Journal of Molecular Sciences among others and has authored various chapters in textbooks including Functional Foods: Principles and Technology. Dr. Killpartrick is finishing his PhD at the University of Vermont in the field of nutrition and food science with a focus on novel methods of nutrient delivery.