Researchers have published the results of a study in Aging Cell, finding some evidence that type 2 diabetes causes accelerated aging.
Later-generation clocks only
This paper begins with explanations of Type 2 diabetes and epigenetic clocks, noting that principal component (PC) versions of clocks may give stronger results because they filter out noise. These researchers eschew first-generation clocks entirely, focusing on GrimAge and PhenoAge along with DunedinPACE, which solely measures age acceleration.
Previous studies have found associations between Type 2 diabetes and aging: One study found that DunedinPACE, which was trained on Western participants, has also found accelerated aging to be associated with diabetes in Taiwanese people [1]. An earlier study by the same researchers found connections between diabetes and aging as measured by other clocks as well [2]. Most importantly, a previous study has found evidence for a causal connection: that it’s diabetes that accelerates aging [3]. These researchers sought to more firmly prove this connection.
A robust cohort
This study used data from the Chinese National Twin Registry (CNTR). A total of 535 pairs of twins (380 pairs identical), including 157 pairs that had both baseline and 4- or 5-year follow-up data (95 pairs identical), were included. These participants were measured for such diabetes-related metrics as fasting glucose and HbA1c along with potential confounders, such as smoking, education, BMI, alcohol consumption, and exercise. This wealth of data allowed the researchers to conduct both cross-sectional and longitudinal analyses.
On average, the participants were 50 years old, and 10% of them had glycemic markers that categorized them as having type 2 diabetes. Among the participants that had follow-up data, almost 12% had type 2 diabetes at baseline and 17% had it at follow-up.
In the cross-sectional study, the researchers found that a couple of measurements related to diabetes, as expected, were strongly associated with age accleration as measured by all three clocks, most notably PhenoAge: people with excess HbA1c had an extra three years of aging on average, according to this clock. Fasting glucose also had a very strong association. Diabetes, itself, was less strongly associated, and did not reach statistical significance in any of the clocks.
A direct longitudinal study did not reveal much additional information. However, a cross-lagged study, which compared measurements at follow-up and at baseline, revealed that people with higher fasting glucose, higher HbA1c, or higher triglyceride and glucose (TyG) indices at baseline were likely to have higher age acceleration according to DunedinPACE at follow-up. The TyG index was associated with higher acceleration according to GrimAge at followup.
Limited, but relevant, evidence
When the analysis was broken down into individual strata, the associations were found to be significant only in men and in people with lower levels of education. This stratification, however, decreases the number of people in these subgroups, which therefore have less statistical power.
While the identical twin pairs eliminated the possibility of different genetic factors leading to different outcomes, the researchers note that their relatively small number, particularly in the group that had both baselines and follow-ups, also hampered this study’s statistical power. However, they were able to come to multiple conclusions, two of the most notable being that DunedinPACE is uniquely sensitive to glycemic metabolism and that these results are not affected by blood cell composition.
In total, while this study provides solid evidence that diabetes accelerates epigenetic aging regardless of confounders, it is still not fully proven, and further research should be conducted to verify this evidence. However, diabetes is still strongly related to early death through a variety of well-known morbidities, such as cardiovascular disease [4].
Literature
[1] Lin, W. Y. (2023). Epigenetic clocks derived from western samples differentially reflect Taiwanese health outcomes. Frontiers in Genetics, 14, 1089819.
[2] Lo, Y. H., & Lin, W. Y. (2022). Cardiovascular health and four epigenetic clocks. Clinical Epigenetics, 14(1), 73.
[3] Kong, L., Ye, C., Wang, Y., Hou, T., Zheng, J., Zhao, Z., … & Wang, T. (2023). Genetic evidence for causal effects of socioeconomic, lifestyle, and cardiometabolic factors on epigenetic-age acceleration. The Journals of Gerontology: Series A, 78(7), 1083-1091.
[4] Palmer, A. K., Gustafson, B., Kirkland, J. L., & Smith, U. (2019). Cellular senescence: at the nexus between ageing and diabetes. Diabetologia, 62, 1835-1841.
