ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Endocrinology of Aging
Remnant Cholesterol Shows Inverse and Nonlinear Associations with Leukocyte Telomere Length and Serum α-Klotho, Mediated by Inflammation and Oxidative Stress
Provisionally accepted
- Peking Union Medical College Hospital, Beijing, China
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Background: Remnant cholesterol (RC) has been implicated in cardiovascular and metabolic disorders, but its direct associations with biological aging remain unclear. We aimed to examine the relationship between RC and two established aging biomarkers, leukocyte telomere length (LTL) and serum α‑Klotho, and to evaluate the potential mediating roles of inflammation and oxidative stress. Methods: This cross-sectional analysis included 1052 adults from a rural cohort in northern China. Linear regressions and restricted cubic splines (RCS) assessed linear and nonlinear relationships. Mediation models explored the mediating effect of inflammation (TNFα, IL-6, IL-1β) and oxidative stress markers (SOD, 8-OHdG). Results: Participants with higher RC levels had lower LTL and α-Klotho levels, along with higher levels of TNFα, IL-6, IL-1β, and SOD. In adjusted linear regression, RC showed negative associations with both LTL and α-Klotho (β[95%CI]: -0.177[-0.262, -0.091] and -0.045[-0.066, -0.024]), independent of conventional lipid profiles. Both relationships were nonlinear (P for nonlinear = 0.001 for LTL; 0.019 for α-Klotho). For LTL, the inverse association was confined to 0.65-1.42 mmol/L (no significant associations outside this range), while for α-Klotho it was observed only below 1.37 mmol/L (no associations above it). TNFα and IL-6 partially mediated the relationship between RC and LTL (17.78% and 14.12%, respectively); while SOD partially mediated the association between RC and α-Klotho (58.18%). Conclusions: RC is inversely and nonlinearly associated with both LTL and α-Klotho, independent of traditional lipid profiles, with inflammation and oxidative stress as partial mediators. From an aging perspective, these cross-sectional findings support increased attention to early RC management alongside traditional lipids.
Keywords: Remnant cholesterol, biological aging, leukocyte telomere length, Serum α-Klotho, Inflammation, Oxidative Stress
Received: 06 Sep 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Xing, Yu, Liu, Gao, Chen, He, Ping, Xu, Li, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huabing Zhang, huabingzhangchn@163.com
Yuxiu Li, liyuxiu@medmail.com.cn
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