With aging, the body’s ability to maintain regular functions declines, increasing susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in immunoglobulin G (IgG) glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of white men from Europe, aged 29–45 years, under treatment with metformin, testosterone, metformin plus testosterone, and placebo (trial registration number NCT02514629, 2013/07/04), and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.

随着年龄的增长，身体维持正常功能的能力下降，增加了对与年龄相关的疾病的易感性。针对衰老潜在生物学变化的治疗干预措施有望预防或延缓多种与年龄相关的疾病。二甲双胍是一种常用于治疗糖尿病的药物，由于其已建立的安全记录以及有关其抗衰老作用的临床前和临床数据，已成为一种潜在的老年治疗剂。糖基化是最常见和最复杂的共翻译和翻译后蛋白质修饰之一，在调节蛋白质功能方面起着至关重要的作用，并与衰老和各种疾病有关。免疫球蛋白 G （IgG） 糖基化模式随年龄增长而发生变化，这些改变可能作为疾病易感性、诊断、治疗监测和整体健康评估的有价值的生物标志物。在这项研究中，我们分析了来自欧洲的 29-45 岁白人男性在二甲双胍、睾酮、二甲双胍加睾酮和安慰剂治疗下的 IgG 糖基化模式（试验注册号 NCT02514629,2013/07/04），并研究了糖基化随时间的纵向变化。我们观察到睾酮治疗和安慰剂组参与者之间 IgG 糖组组成的统计学显着差异，无乳糖基化减少，半乳糖基化和唾液酸化增加。然而，二甲双胍治疗未导致糖基化模式的统计学显着变化。 这些发现有助于我们了解治疗干预对 IgG 糖基化的影响，并证实 IgG 糖基化作为一种重要生物标志物的价值，能够使用 GlycanAge 指数评估生物年龄，并提供与实际年龄相比的整体健康状况的见解。