Department of Reproductive Medical Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Sichuan University, Chengdu, Sichuan, China.
Front Endocrinol (Lausanne). 2024 Apr 2;15:1370457. doi: 10.3389/fendo.2024.1370457. eCollection 2024.
Serum Klotho (S-Klotho) is a transmembrane protein holds pivotal roles in anti-aging. The Dietary Inflammation Index (DII), a meticulously dietary tool, quantifies the inflammatory potential of an individual's diet. The existing research strongly suggests that a low DII diet plays a significant role in delaying aging and reducing aging-related symptoms in males. Testosterone could potentially act as a mediating intermediary between DII and S-Klotho. However, this aspect remains unexplored. This study aims to investigate the potential causal link of testosterone between DII and S-Klotho in males.
We utilized data from National Health and Nutrition Examination Survey (NHANES) which focused on male participants from 2013-2016. Mediation analyses were used to investigate the effects of testosterone (TT), free testosterone (FT), and free androgen index (FAI) on the DII-S-Klotho relationship, using three modes adjusting for covariates.
Mediation analysis unveiled a significant inverse correlation between DII and S-Klotho levels (model 1: c = -14.78, p = 0.046). The interaction between DII and S-Klotho was modulated by TT in model 1 (ab = -1.36; 95% CI: -5.59, -0.55; p = 0.008), but lost significance after adjustments (model 2: ab = -0.39; 95% CI: -4.15, 1.66; p = 0.378; model 3: ab = -0.59; 95% CI: -4.08, 2.15; p = 0.442). For FT, the mediating impact was not statistically significant (model 1: ab = 0.43; 95% CI: -0.51, 5.44; p = 0.188; model 2: ab = 0.72; 95% CI: -0.26, 5.91; p = 0.136; model 3: ab = 0.84; 95% CI: -0.02, 8.06; p = 0.056). Conversely, FAI consistently influenced the DII-S-Klotho relationship (model 1: ab = 2.39; 95% CI: 0.69, 9.42; p = 0.002), maintaining significance after adjustments (model 2: ab = 3.2; 95% CI: 0.98, 11.72; p = 0.004; model 3: ab = 3.15; 95% CI: 0.89, 14.51; p = 0.026).
This study observed no mediating influence of TT or FT on the correlation between DII and S-Klotho after covariate control. Remarkably, FAI continued to significantly mediate the DII-S-Klotho connection even following covariate adjustment, although its significance in males warrants careful consideration.
血清 Klotho（S-Klotho）是一种跨膜蛋白，在抗衰老方面起着关键作用。饮食炎症指数（DII）是一种精细的饮食工具，可量化个体饮食的炎症潜力。现有研究强烈表明，低 DII 饮食在延缓衰老和减少男性与衰老相关的症状方面发挥着重要作用。睾酮可能是 DII 和 S-Klotho 之间的中介介质。然而，这方面仍有待探索。本研究旨在探讨睾酮在男性 DII 和 S-Klotho 之间可能存在的因果关系。
我们利用了 2013-2016 年全国健康和营养检查调查（NHANES）中男性参与者的数据。使用三种模式进行中介分析，以调查睾酮（TT）、游离睾酮（FT）和游离雄激素指数（FAI）对 DII-S-Klotho 关系的影响，同时调整了协变量。
中介分析揭示了 DII 和 S-Klotho 水平之间存在显著的负相关（模型 1：c = -14.78，p = 0.046）。DII 和 S-Klotho 之间的相互作用在模型 1 中受到 TT 的调节（ab = -1.36；95%CI：-5.59，-0.55；p = 0.008），但在调整后失去了意义（模型 2：ab = -0.39；95%CI：-4.15，1.66；p = 0.378；模型 3：ab = -0.59；95%CI：-4.08，2.15；p = 0.442）。对于 FT，中介作用没有统计学意义（模型 1：ab = 0.43；95%CI：-0.51，5.44；p = 0.188；模型 2：ab = 0.72；95%CI：-0.26，5.91；p = 0.136；模型 3：ab = 0.84；95%CI：-0.02，8.06；p = 0.056）。相反，FAI 一直影响着 DII-S-Klotho 之间的关系（模型 1：ab = 2.39；95%CI：0.69，9.42；p = 0.002），在调整协变量后仍保持显著（模型 2：ab = 3.2；95%CI：0.98，11.72；p = 0.004；模型 3：ab = 3.15；95%CI：0.89，14.51；p = 0.026）。
本研究观察到在控制协变量后，TT 或 FT 对 DII 和 S-Klotho 之间的相关性没有中介影响。值得注意的是，即使在调整协变量后，FAI 仍然显著调节 DII-S-Klotho 之间的联系，尽管其在男性中的意义需要谨慎考虑。
