METHODS: We conducted a Mendelian randomization (MR) study using published GWAS summary statistics. Aging biomarkers included telomere length (qPCR), facial aging (subjective evaluation), and epigenetic age markers (HannumAge, IEAA, GrimAge, PhenoAge). The frailty index was calculated from clinical assessments, and cognitive performance was evaluated with standardized tests. Analyses included Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median (WM) methods, adjusted for multiple comparisons.
RESULTS: CM was significantly associated with shorter telomere length (IVW: β = - 0.1, 95% CI - 0.18 to - 0.02, pFDR = 0.032) and increased HannumAge (IVW: β = 1.33, 95% CI 0.36 to 2.3, pFDR = 0.028), GrimAge (IVW: β = 1.19, 95% CI 0.19 to 2.2, pFDR = 0.040), and PhenoAge (IVW: β = 1.4, 95% CI 0.12 to 2.68, pFDR = 0.053). A significant association was also found with the frailty index (IVW: β = 0.31, 95% CI 0.13 to 0.49, pFDR = 0.006). No significant associations were found with facial aging, IEAA, or cognitive performance.
CONCLUSIONS: CM is linked to accelerated biological aging, shown by shorter telomere length and increased epigenetic aging markers. CM was also associated with increased frailty, highlighting the need for early interventions to mitigate long-term effects. Further research should explore mechanisms and prevention strategies.
方法:我们使用已发表的GWAS汇总统计进行了孟德尔随机化(MR)研究。老化的生物标志物包括端粒长度(qPCR),面部老化(主观评价),和表观遗传年龄标记(HannumAge,IEAA,GrimAge,PhenoAge).虚弱指数是根据临床评估计算的,并通过标准化测试评估认知表现。分析包括逆方差加权(IVW),Egger先生,和加权中值(WM)方法,针对多重比较进行了调整。
结果:CM与端粒长度较短(IVW:β=-0.1,95%CI-0.18至-0.02,pFDR=0.032)和汉诺年龄增加(IVW:β=1.33,95%CI0.36至2.3,pFDR=0.028)显着相关,GrimAge(IVW:β=1.19,95%CI0.19至2.2,pFDR=0.040),和表型(IVW:β=1.4,95%CI0.12至2.68,pFDR=0.053)。还发现与虚弱指数显着相关(IVW:β=0.31,95%CI0.13至0.49,pFDR=0.006)。没有发现与面部老化的显著关联,IEAA,或认知表现。
结论:CM与加速的生物衰老有关,端粒长度较短,表观遗传衰老标记增加。CM也与虚弱增加有关,强调需要早期干预以减轻长期影响。进一步的研究应探索机制和预防策略。