Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China.
Aging Clin Exp Res. 2024 Nov 29;36(1):227. doi: 10.1007/s40520-024-02877-6.
The gut microbiota is closely related to aging, but the genetic relationship between gut microbiota and aging has not been well investigated. The aim of the study was to explore the association of microbiota with epigenetic age acceleration (EAA) using the Mendelian randomization.
The independent genetic instruments of gut microbiota were obtained from MiBioGen consortium and the Dutch Microbiome Project. EAA data were derived from genome-wide association study. To assess the causal relationship between gut microbiota and EAA, we applied four different methods of Mendelian Randomization (MR) analysis: the inverse variance weighted method (IVW), the MR-Egger regression, the weighted median analysis (WMA), and the weighted mode. Furthermore, sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.
We identified potential causal associations between 12 bacterial taxa and EAA (P and P < 0.05). Among them, species Holdemania_unclassified (OR: 1.31, 95% CI: 1.13-1.52, P = 0.0004) retained a strong positive association with GrimAge acceleration. Family Acidaminococcaceae (OR: 0.64, 95% CI: 0.44-0.93, P = 0.019) and family Clostridiaceae1 (OR: 0.69, 95% CI: 0.49-0.97 P = 0.031) were negative association with GrimAge acceleration. Reverse MR analyses indicated that EAA was associated with 6 bacterial taxa in IVW and WMA. Among them, a strong inverse association was found between Phenoage acceleration and genus Turicibacter (OR: 0.928, 95%CI: 0.888-0.971, P and P < 0.001).
Our study implicates the potential causal effects of specific microbiota on EAA, potentially providing novel insights into the prevention aging through specific gut microbiota.
肠道微生物群与衰老密切相关，但肠道微生物群与衰老之间的遗传关系尚未得到很好的研究。本研究旨在使用孟德尔随机化方法探讨微生物群与表观遗传年龄加速（EAA）的关联。
从 MiBioGen 联盟和荷兰微生物组计划中获得了肠道微生物群的独立遗传工具。EAA 数据源自全基因组关联研究。为了评估肠道微生物群与 EAA 之间的因果关系，我们应用了孟德尔随机化（MR）分析的四种不同方法：逆方差加权法（IVW）、MR-Egger 回归、加权中位数分析（WMA）和加权模式。此外，还进行了敏感性分析以评估异质性和水平多效性。
我们确定了 12 种细菌与 EAA 之间存在潜在的因果关联（P 和 P < 0.05）。其中，种属 Holdemania_unclassified（OR：1.31，95%CI：1.13-1.52，P = 0.0004）与 GrimAge 加速呈强烈正相关。科 Acidaminococcaceae（OR：0.64，95%CI：0.44-0.93，P = 0.019）和科 Clostridiaceae1（OR：0.69，95%CI：0.49-0.97，P = 0.031）与 GrimAge 加速呈负相关。反向 MR 分析表明，EAA 在 IVW 和 WMA 中与 6 种细菌相关。其中，Phenoage 加速与属 Turicibacter 之间存在强烈的负相关（OR：0.928，95%CI：0.888-0.971，P 和 P < 0.001）。
本研究提示特定微生物群对 EAA 存在潜在的因果影响，这可能为通过特定肠道微生物群预防衰老提供新的见解。
