BackgroundCytokines and growth factors may serve as a bridge in studying the causal relationships between inflammaging and sarcopenia due to their roles in inflammaging. In this study, we aim to explore the causal association of cytokines with sarcopenia and aging traits and further identify the significant inflammation factors.MethodsBidirectional Mendelian randomization (MR) analysis was used to identify the causality. Forty‐one kinds of circulation cytokines and growth factors were set as exposures, and the data were from a summary genome‐wide association study (GWAS) containing three cohorts with 8293 healthy participants of European ancestry from 1983 to 2011. Hand grip strength, adjusted appendicular lean mass (AALM), usual walking pace, moderate‐to‐vigorous physical activity (MVPA) levels, able to walk or cycle unaided for 10 min (AWCU10) and telomere length were selected as outcomes. Data for outcomes were obtained from meta‐GWAS and the UK Biobank, and sample sizes ranged from 69 537 to 472 174. Low hand grip strength was defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) cut‐off points, respectively. Other outcome traits were defined and measured according to the UK Biobank and raw cohorts' criteria. We set two significance thresholds for single nucleotide polymorphisms (SNPs) associated with exposures to obtain adequate SNPs (5 × 10−6 and 5 × 10−8). Inverse‐variance weighted, MR‐Egger and weighted median were employed to estimate the causality.ResultsTwenty‐seven factors were identified to relate to sarcopenia and aging traits causally, and most were associated with only one outcome trait. IL16 (interleukin‐16), CTACK (cutaneous T‐cell attracting chemokine), MIP1b (macrophage inflammatory protein 1b) and PDGFbb (platelet‐derived growth factor BB) were proven to relate causally to at least one sarcopenia and aging trait in both analyses with two significance thresholds. IL16 was causally associated with hand grip strength (0.977 [0.956–0.998] for EWGSOP and 0.933 [0.874–0.996] for FNIH), AALM (0.991 [0.984, 0.998]), MVPA (0.997 [0.995–1.000]) and AWCU10 (1.008 [1.003–1.013]). CTACK was proven to relate causally to hand grip strength (1.013 [1.007–1.019] for EWGSOP and 1.090 [1.041–1.142] for FNIH), AWCU10 (0.990 [0.986–0.994]) and telomere length (0.998 [0.983–0.994]). The results indicated that MIP1b has a causal effect on hand grip strength (1.032 [1.001–1.063] for EWGSOP), AWCU10 (0.994 [0.988–1.000] and 0.993 [0.988–0.998]) and telomere length (1.006 [1.000–1.012]). PDGFbb may causally relate to AALM (1.016 [1.001–1.030]) and telomere length (1.011 [1.007–1.015]). Reserve MR analyses also proved their unidirectional causal effects.ConclusionsTwenty‐seven factors were causally related to sarcopenia and aging traits, and the causal effects of IL16, CTACK, MIP1b and PDGFbb were proven in both analyses with two significance thresholds.

中文翻译：

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绘制细胞因子与肌肉减少症和衰老特征的因果关系：双向孟德尔随机化的证据

背景细胞因子和生长因子由于它们在炎症中的作用，可以作为研究炎症和肌肉减少症之间因果关系的桥梁。在本研究中，我们旨在探讨细胞因子与肌肉减少症和衰老特征的因果关系，并进一步确定显着的炎症因素。方法采用双向孟德尔随机化（MR）分析来确定因果关系。将 41 种循环细胞因子和生长因子设置为暴露量，数据来自一项总结性全基因组关联研究 (GWAS)，该研究包含 1983 年至 2011 年间包含 8293 名欧洲血统健康参与者的三个队列。选择阑尾瘦体重 (AALM)、通常步行速度、中度至剧烈体力活动 (MVPA) 水平、能够独立步行或骑自行车 10 分钟 (AWCU10) 和端粒长度作为结果。结果数据来自 meta-GWAS 和英国生物银行，样本量范围为 69 537 至 472 174。低握力由欧洲老年人肌少症工作组 (EWGSOP) 和国家研究所基金会定义健康 (FNIH) 分界​​点，分别。其他结果特征是根据英国生物银行和原始队列的标准定义和测量的。我们为与暴露相关的单核苷酸多态性 (SNP) 设置了两个显着性阈值，以获得足够的 SNP (5 × 10−6和 5 × 10−8）。采用逆方差加权、MR-Egger 和加权中位数来估计因果关系。 结果 确定了 27 个与肌肉减少症和衰老特征存在因果关系的因素，其中大多数仅与一种结果特征相关。两项分析均证明 IL16（白细胞介素 16）、CTACK（皮肤 T 细胞吸引趋化因子）、MIP1b（巨噬细胞炎症蛋白 1b）和 PDGFbb（血小板衍生生长因子 BB）与至少一种肌肉减少症和衰老特征存在因果关系有两个显着性阈值。 IL16 与握力（EWGSOP 为 0.977 [0.956–0.998]，FNIH 为 0.933 [0.874–0.996]）、AALM（0.991 [0.984, 0.998]）、MVPA（0.997 [0.995–1.000]）和 AWCU10（ 1.008 [1.003–1.013]）。 CTACK 被证明与握力（EWGSOP 为 1.013 [1.007–1.019]，FNIH 为 1.090 [1.041–1.142]）、AWCU10 (0.990 [0.986–0.994]) 和端粒长度 (0.998 [0.983–0.994]) 存在因果关系。结果表明，MIP1b 对握力（EWGSOP 为 1.032 [1.001–1.063]）、AWCU10（0.994 [0.988–1.000] 和 0.993 [0.988–0.998]）和端粒长度（1.006 [1.000–1.012]）有因果影响。 ）。 PDGFbb 可能与 AALM (1.016 [1.001–1.030]) 和端粒长度 (1.011 [1.007–1.015]) 存在因果关系。储备MR分析也证明了它们的单向因果效应。结论27个因素与肌肉减少症和衰老特征存在因果关系，IL16、CTACK、MIP1b和PDGFbb的因果效应在两项分析中均得到了两个显着性阈值的证明。