Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 27;17(1):146.
doi: 10.1186/s12920-024-01914-7.

Epigenetic age acceleration is associated with blood lipid levels in a multi-ancestry sample of older U.S. adults

Lisha Lin #  1 , Jenna Kiryakos #  1 , Farah Ammous  2 , Scott M Ratliff  1 , Erin B Ware  2 , Jessica D Faul  2 , Sharon L R Kardia  1 , Wei Zhao  1   2 , Kira S Birditt  2 , Jennifer A Smith  3   4
Affiliations

Epigenetic age acceleration is associated with blood lipid levels in a multi-ancestry sample of older U.S. adults

Lisha Lin et al. BMC Med Genomics. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Aging; Cholesterol; DNA methylation; Epigenetic age acceleration; HDL cholesterol; LDL cholesterol; Lipids; Triglycerides.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests, except that J. A. Smith is a member of the editorial board for BMC Medical Genomics.

Figures

Fig. 1
Fig. 1
Plots of predicted blood lipid levels by DunedinPACE at the 25th (62 years) and 75th percentile (77 years) of age (top panels), sex (middle panels) and college degree (bottom panels). TC, total cholesterol; HDL-C, high-density lipoprotein; TG, triglycerides Interaction model: blood lipid level ~ epigenetic age acceleration + age at methylation measurement + sex + race/ethnicity + fasting status + lipid-lowering medication use + body mass index + smoking status + high school degree or equivalent + college degree and above + DunedinPACE × demographic factor Only interactions with DunedinPACE and demographic factors with Pinteraction < 0.05 in the interaction model are shown. Age was centered for the interaction analysis. The line and corresponding confidence intervals represent the predicted blood lipid level at the corresponding value of DunedinPACE
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

References

    1. Shah NS, Lloyd-Jones DM, O’Flaherty M, Capewell S, Kershaw KN, Carnethon M, et al. Trends in Cardiometabolic Mortality in the United States, 1999–2017. JAMA. 2019;322(8):780–2. doi: 10.1001/jama.2019.9161. - DOI - PMC - PubMed
    1. Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care. 2013;40(1):195–211. doi: 10.1016/j.pop.2012.11.003. - DOI - PMC - PubMed
    1. Karantas ID, Okur ME, Okur NÜ, Siafaka PI. Dyslipidemia management in 2020: an update on diagnosis and therapeutic perspectives. Endocrine, metabolic & Immune disorders-drug targets (formerly current drug targets-Immune. Endocr Metabolic Disorders) 2021;21(5):815–34. - PubMed
    1. Handelsman Y, Jellinger PS, Guerin CK, Bloomgarden ZT, Brinton EA, Budoff MJ, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm–2020 executive summary. Endocr Pract. 2020;26(10):1196–224. doi: 10.4158/CS-2020-0490. - DOI - PubMed
    1. Otocka-Kmiecik A, Mikhailidis DP, Nicholls SJ, Davidson M, Rysz J, Banach M. Dysfunctional HDL: a novel important diagnostic and therapeutic target in cardiovascular disease? Prog Lipid Res. 2012;51(4):314–24. doi: 10.1016/j.plipres.2012.03.003. - DOI - PubMed
-