数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
研究问题
Aging, as a complex and irreversible biological process, is not only a core risk factor for numerous chronic dis- eases but also directly leads to physiological decline and increased mortality rates [1, 2].
方法
MR study design and data sources We implemented the drug-target MR approach to assess causality [18].；[21], which included 6,195 individuals of African American descent.；Four EAA biomarkers (HorvathAA, HannumAA, Phe- noAA, and GrimAA) were quantified as the residuals from the regression of DNAm age onto chronological age.；The weighted median method [23] and MR-Egger regression method [24] were used as comple- mentary analyses.
核心结论
Specifically, each 1-SD increase in genetically predicted ESR1 expression was causally associated with a 1.26-SD reduction in PhenoAA (β =−1.26; 95% CI,−2.16 to−0.37; Fig.；The study included a total of 673 postmenopausal women, of whom 206 (30.6%) received HRT.；Compared with the non-HRT group, the HRT group was significantly younger and had lower PhenoAA, GrimAA, and Grim2AA (all P<0.05). ‖ 结论：In conclusion, estrogens may decelerate phenotypic epigenetic aging (PhenoAA) via the ESR1 pathway.
局限
Several key limitations of this study warrant acknowl- edgment.；Accordingly, the significant retarding effect of ESR1 expression on Phe- noAA observed in this study is more likely a conservative underestimate than a spurious association, though the precise magnitude of the effect should still be interpreted with caution.；Second, selection bias may have been intro- duced because our analysis was restricted to postmeno- pausal participants with complete biological, clinical, and covariate data.
对本项目的价值
★★★★☆ 生物学年龄读数是选择替代终点的主要候选，直接影响终点设计与样本量估算。命中核心 表观时钟；队列：NHANES；最大样本量约 31,684；设计 孟德尔随机化、Meta 分析。
全文来源
BMC OA PDF（正文 59,369 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Hormone replacement therapy through the lens of epigenetic clock: estrogen signals, glycemic status, and lifespan.
- 期刊与标识：Biol Sex Differ · PMID 42947173 · DOI 10.1186/s13293-026-00959-w**
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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