Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, USA.
Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson St, Ann Arbor, MI, 48104, USA.
BMC Med Genomics. 2024 May 27;17(1):146. doi: 10.1186/s12920-024-01914-7.
Dyslipidemia, which is characterized by an unfavorable lipid profile, is a key risk factor for cardiovascular disease (CVD). Understanding the relationships between epigenetic aging and lipid levels may help guide early prevention and treatment efforts for dyslipidemia.
We used weighted linear regression to cross-sectionally investigate the associations between five measures of epigenetic age acceleration estimated from whole blood DNA methylation (HorvathAge Acceleration, HannumAge Acceleration, PhenoAge Acceleration, GrimAge Acceleration, and DunedinPACE) and four blood lipid measures (total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG)) in 3,813 participants (mean age = 70 years) from the Health and Retirement Study (HRS). As a sensitivity analysis, we examined the same associations in participants who fasted prior to the blood draw (n = 2,531) and in participants who did not take lipid-lowering medication (n = 1,869). Using interaction models, we also examined whether demographic factors including age, sex, and educational attainment modified the relationships between epigenetic age acceleration and blood lipids.
After adjusting for age, race/ethnicity, sex, fasting status, and lipid-lowering medication use, greater epigenetic age acceleration was associated with lower TC, HDL-C, and LDL-C, and higher TG (p < 0.05), although the effect sizes were relatively small (e.g., < 7 mg/dL of TC per standard deviation in epigenetic age acceleration). GrimAge acceleration and DunedinPACE associations with all lipids remained significant after further adjustment for body mass index, smoking status, and educational attainment. These associations were stronger in participants who fasted and who did not use lipid-lowering medication, particularly for LDL-C. We observed the largest number of interactions between DunedinPACE and demographic factors, where the associations with lipids were stronger in younger participants, females, and those with higher educational attainment.
Multiple measures of epigenetic age acceleration are associated with blood lipid levels in older adults. A greater understanding of how these associations differ across demographic groups can help shed light on the relationships between aging and downstream cardiovascular diseases. The inverse associations between epigenetic age and TC and LDL-C could be due to sample limitations or non-linear relationships between age and these lipids, as both TC and LDL-C decrease faster at older ages.
血脂异常表现为血脂谱异常，是心血管疾病（CVD）的一个关键危险因素。了解表观遗传衰老与血脂水平之间的关系，可能有助于指导血脂异常的早期预防和治疗。
我们使用加权线性回归方法，在横断面研究中，分析了从全血 DNA 甲基化中估算的 5 种表观遗传年龄加速（HorvathAgeAcceleration、HannumAgeAcceleration、PhenoAgeAcceleration、GrimAgeAcceleration 和 DunedinPACE）与 3813 名（平均年龄 70 岁）健康与退休研究（HRS）参与者的 4 种血脂指标（总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG））之间的关系。作为敏感性分析，我们在之前采血前禁食的 2531 名参与者和未服用降脂药物的 1869 名参与者中，检验了相同的关联。通过交互模型，我们还检验了年龄、性别和教育程度等人口统计学因素是否改变了表观遗传年龄加速与血脂之间的关系。
在调整年龄、种族/民族、性别、禁食状态和降脂药物使用后，较大的表观遗传年龄加速与 TC、HDL-C 和 LDL-C 降低及 TG 升高有关（p<0.05），尽管效应大小相对较小（例如，TC 每标准偏差的表观遗传年龄加速增加约 7mg/dL）。在进一步调整体重指数、吸烟状况和教育程度后，GrimAge 加速和 DunedinPACE 与所有脂质的关联仍然显著。在禁食和未服用降脂药物的参与者中，这些关联更强，尤其是 LDL-C。我们观察到 DunedinPACE 与人口统计学因素之间存在最多的相互作用，这些关联在年轻参与者、女性和教育程度较高的参与者中更强。
多种表观遗传年龄加速指标与老年人的血脂水平相关。更好地了解这些关联在不同人群中的差异，可以帮助我们了解衰老与下游心血管疾病之间的关系。表观遗传年龄与 TC 和 LDL-C 呈负相关，可能是由于样本限制或年龄与这些脂质之间的非线性关系，因为 TC 和 LDL-C 在较老的年龄下降得更快。
