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Epigenetic clocks are algorithms that are based on the methylation patterns at different points on the genome, and have been used to predict biological age.
These are fairly new uses of machine learning, and not many studies have been done to determine whether they can detect aging caused by lifestyle factors.
In a study by UC San Francisco researchers, the effect of diet on epigenetic aging has been measured in a cohort of Black women for the first time.
This study used the GrimAGE2 clock, which its developers say has been validated using cohorts from different ancestries.
According to a recent study outlined in JAMA Network Open, sugar intake increases an epigenetic measure of biological age in women, while adherence to diets high in antioxidants or anti-inflammatory foods decreases it.
JAMA Network Open
Researchers from UC San Francisco followed up a cohort of Black and white female participants of the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS).
Participants were those who had initially enrolled between the ages of 9 and 19 from 1987-1997 and were followed up between 2015-2019, when they were aged 36-43 years. The study was initially designed to investigate heart and metabolic health, and data on diet were available due to participants being asked to complete a 3-day food diary at follow-up.
The amount of added sugar in the diet was calculated using this data, as was adherence to the Mediterranean diet, the Alternate Healthy Eating Index and a new nutrient score from 0-24, designed specifically for this study.
This new nutrient index was calculated using data on the quantity of the following micronutrients in the diet including:
vitamin A
vitamin E
vitamin C
folate
vitamin B12
zinc
selenium
magnesium
fiber
monounsaturated fatty acids
isoflavones
sugar.
How diet influences epigenetic age
Epigenetic data on 342 participants was collected using a saliva sample. Half of the participants were Black and half were white.
Epigenetic age was calculated using an algorithm called GrimAGE2. This looks at methylation of particular points on the genome to estimate exposure to c-reactive protein, a protein made in the liver in response to inflammation, and hemoglobin A1C, which shows how much sugar has been in the blood.
GrimAGE2
Researchers discovered that for each additional gram of sugar people ate a day, there was an increase of 7 days in their GrimAGE2 score. They also found that participants who adhered to a Mediterranean diet, the Alternate Healthy Eating Index and the researchers’ own nutrient index had lower GrimAGE2 scores.
Authors say their results are consistent with previous studies, and highlight that this is the first study to look at the effect of diet on the epigenetic age of Black women.
They suggest that higher quality diet with greater amounts of antioxidants and anti-inflammatory nutrients have a positive impact on epigenetic age, whereas sugar increases epigenetic age.
A limitation of the study is that GrimAGE2 was originally trained on individuals aged 40-92, and the cohort that were investigated for this study were slightly younger, with an average age of 39.2.
However, Lorna Harries, PhD, a professor of molecular genetics at the University of Exeter College of Medicine and Health in the United Kingdom, who was not involved in the research, told Medical News Today that aging clocks were “very useful.”
Lorna Harries, PhD
“Presently, they remain one of the very few tools we have which allow us to measure aging at the level of cells and molecules in living people. If we are to develop interventions that interact with cellular ageing, we need tools to be able to measure the effect of our interventions in living people. One thing to remember, though, is that different clocks such as GrimAGE or the methylation clocks may be measuring different aspects of cell physiology, not all of which will link directly to functional outcomes.”
– Lorna Harries, PhD
What is the relationship between inflammation and blood sugar?
GrimAGE2 is a machine-learning based epigenetic clock that was developed to specifically calculate exposure of the genome to inflammation and a blood glucose marker to infer epigenetic age.
Both of these play an interconnected role in aging. The study did not, however, investigate potential mechanisms.
Harries suggested that: “Things that mess with your metabolism — [for example,] too much sugar, too much fat — can set up a situation where cells become stressed, and stressed cells can age faster, or acquire traits such as the production of inflammatory factors that contribute to cellular and systemic aging.“
“High levels of sugar in the blood can also lead to advanced glycation end products, which can drive inflammation. All of these factors can feed into changes in cells and systems which result in faster aging at the cellular and, ultimately, systemic level,” she explained.
Kubanych Takyrbashev, MD, a health and wellness advisor at NAO, not involved in this study, told MNT: “In my [own] research, I’ve found that when blood sugar levels are consistently elevated, glucose molecules can bind to proteins in glycation.“
“This creates harmful compounds called AGEs that accumulate in tissues and accelerate cellular aging,“ he explained.
“Based on my clinical experience, high sugar intake increases the production of free radicals, leading to oxidative damage to DNA, proteins, and lipids. This damage accumulates over time and contributes to premature aging of cells and tissues,” said Takyrbashev.
While results for this study were adjusted for a number of factors, the average BMI of the cohort was high at 32.5, which correlates with obesity.
Harries said: “Things like BMI are usually controlled for as confounders. However, it is not always possible to adjust away all the confounding, so it’s possible that there may be a residual effect, since BMI is tightly linked with insulin resistance, a known cause of cellular aging.”