■端粒已被认为是加速衰老的生物标志物,端粒长度(TL)缩短与多种慢性疾病密切相关。在观察性研究中,人血清代谢物与TL维持或缩短密切相关。然而,对潜在的病理机制知之甚少,和孟德尔随机化(MR)分析血清代谢物可能提供一个更全面的了解潜在的生物过程。
■我们采用了双样本MR分析方法来评估486种血清代谢物与TL之间的因果关系。我们应用了逆方差加权(IVW)方法作为我们的主要分析,并确保我们的结果的稳定性和鲁棒性,其他分析方法,包括加权中位数,MR-Egger,并进行了加权模式。MR-Egger截距测试用于检测多效性。实施Cochran的Q检验来量化异质性的程度。此外,我们进行了通路分析,以确定潜在的代谢通路.
■我们确定了11种与TL相关的已知血液代谢物。在这些代谢物中,四个是脂质(牛磺胆酸盐,十二烷二酸,5,8-十四碳二烯酸酯,和15-甲基棕榈酸酯),一种氨基酸(乙酰丙酸(4-氧戊酸)),一种碳水化合物(乳酸),一个核苷酸(假尿苷),一种能量(磷酸盐),和三种外源性物质(硫酸2-羟基对乙酰氨基酚,对黄嘌呤,和麦角硫因)。已知的保护性代谢物包括乙酰丙酸酯(4-氧戊酸盐),十二烷二酸,5,8-十四碳二烯酸酯,乳酸,磷酸盐,对黄嘌呤,和麦角硫因.已鉴定多种代谢途径与端粒长度的维持有关。
■我们的MR分析提供了暗示性证据,支持11种已鉴定的血液代谢物与TL之间的因果关系,需要进一步探索以阐明这些血清代谢物和代谢途径可能影响端粒进展的机制。
UNASSIGNED: Telomere has been recognized as a biomarker of accelerating aging, and telomere length (TL) shortening is closely related to diverse chronic illnesses. Human serum metabolites have demonstrated close correlations with TL maintenance or shortening in observational studies. Nevertheless, little is known about the underlying pathological mechanisms, and Mendelian randomization (MR) analysis of serum metabolites may provide a more comprehensive understanding of the potential biological process.
UNASSIGNED: We employed a two-sample MR analysis method to assess the causal links between 486 serum metabolites and TL. We applied the inverse-variance weighted (IVW) approach as our primary analysis, and to assure the stability and robustness of our results, additional analysis methods including the weighted median, MR-Egger, and weighted mode were conducted. MR-Egger intercept test was utilized to detect the pleiotropy. Cochran\'s Q test was implemented to quantify the extent of heterogeneity. Furthermore, the pathway analysis was conducted to identify potential metabolic pathways.
UNASSIGNED: We identified 11 known blood metabolites associated with TL. Among these metabolites, four were lipid (taurocholate, dodecanedioate, 5,8-tetradecadienoate, and 15-methylpalmitate), one amino acid (levulinate (4-oxovaleate)), one carbohydrate (lactate), one nucleotide (pseudouridine), one energy (phosphate), and three xenobiotics (2-hydroxyacetaminophen sulfate, paraxanthine, and ergothioneine). The known protective metabolites included levulinate (4-oxovaleate), dodecanedioate, 5,8-tetradecadienoate, lactate, phosphate, paraxanthine, and ergothioneine. Multiple metabolic pathways have been identified as being implicated in the maintenance of telomere length.
UNASSIGNED: Our MR analysis provided suggestive evidence supporting the causal relationships between 11 identified blood metabolites and TL, necessitating further exploration to clarify the mechanisms by which these serum metabolites and metabolic pathways may affect the progression of telomeres.