Dyslipidemia and aging: the non-linear association between atherogenic index of plasma (AIP) and aging acceleration

Cardiovasc Diabetol. 2025 Apr 25;24(1):181. doi: 10.1186/s12933-025-02695-8.

Abstract

Background: Dyslipidemia has been proved to play a pivotal role in biological aging. Atherogenic Index of Plasma (AIP), derived from serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), is an effective biomarker of dyslipidemia. However, whether AIP can be used as an indicator of biological aging remains unclear. This study aims to investigate the relationship between AIP and biological aging in the US adult population.

Methods: 4,471 American adults with age over 20 years from the National Health and Nutrition Examination Survey (NHANES) database were included in this study. Biological aging was assessed by phenotypic age acceleration (PhenoAgeAccel). Multivariable linear regression models, subgroup analyses and interaction tests were employed to explore the association between AIP and PhenoAgeAccel. Furthermore, adjusted restricted cubic spline (RCS) analyses were employed to assess potential nonlinear relationships, while mediation analysis was utilized to identify the mediating effects of homeostatic model assessment of insulin resistance (HOMA-IR). Besides, network pharmacology was performed to determine the potential mechanisms underlying dyslipidemia-related aging acceleration.

Results: A total of 4,471 participants were included in this study, the median chronological age, PhenoAge and PhenoAgeAccel for the overall population were 49 (35-64) years, 42.85 (27.30-59.68) years, and - 6.92 (- 10.52 to -2.46) years, respectively. In the fully adjusted model, one unit increase of AIP was correlated with 1.820-year increase in PhenoAgeAccel (β = 1.820, 95% CI: 1.085-2.556), which was more pronounced among individuals being female, diabetic and hypertensive. Furthermore, RCS analysis revealed a nonlinear relationship between AIP and PhenoAgeAccel, with an inflection point identified at -0.043 for AIP via threshold and saturation effect analysis. AIP demonstrated a positive correlation with PhenoAgeAccel both before (β = 6.550, 95% CI: 5.070-8.030) and after (β = 3.898, 95% CI: 2.474-5.322) this inflection point. Additionally, HOMA-IR was found to mediate 39.21% of the association between AIP and PhenoAgeAccel. Finally, network pharmacology analysis identified INS, APOE, APOB, IL6, IL10, PPARG, MTOR, ACE, PPARGC1A, and SERPINE1 as core targets in biological aging, which were functionally linked to key signaling pathways like AMPK, apelin, JAK-STAT, FoxO, etc. CONCLUSIONS: An elevated AIP was notably and positively correlated with accelerated aging, suggesting that AIP may serve as an effective predictor to evaluate accelerated aging.

Keywords: Accelerated aging; Atherogenic index of plasma; Dyslipidemia; PhenoAgeAccel.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aging* / blood
  • Atherosclerosis* / blood
  • Atherosclerosis* / diagnosis
  • Atherosclerosis* / epidemiology
  • Biomarkers / blood
  • Cholesterol, HDL* / blood
  • Cross-Sectional Studies
  • Databases, Factual
  • Dyslipidemias* / blood
  • Dyslipidemias* / diagnosis
  • Dyslipidemias* / epidemiology
  • Female
  • Humans
  • Insulin Resistance
  • Male
  • Middle Aged
  • Nonlinear Dynamics
  • Nutrition Surveys
  • Phenotype
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Triglycerides* / blood
  • United States / epidemiology
  • Young Adult

Substances

  • Biomarkers
  • Triglycerides
  • Cholesterol, HDL