表观遗传因素与炎症衰老：FOXO3A作为肌肉减少症的潜在生物标志物以及老年人中DNMT3A和SIRT3的上调
Epigenetic factors and inflammaging: FOXO3A as a potential biomarker of sarcopenia and upregulation of DNMT3A and SIRT3 in older adults.
作者信息
Bogucka Diana, Wajda Anna, Stypińska Barbara, Radkowski Marcin Jerzy, Targowski Tomasz, Modzelewska Ewa, Kmiołek Tomasz, Ejma-Multański Adam, Filipowicz Gabriela, Kaliberda Yana, Dudek Ewa, Paradowska-Gorycka Agnieszka
机构信息
Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Department of Geriatrics, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
出版信息
Front Immunol. 2025 Feb 17;16:1467308. doi: 10.3389/fimmu.2025.1467308. eCollection 2025.
BACKGROUND
Epigenetic factors influence inflammaging and geriatric disorders such as sarcopenia and frailty. It is necessary to develop a biomarker/panel of biomarkers for fast and easy diagnostics. Currently, hard-to-access equipment is required to diagnose sarcopenia. The development of a biomarker/panel of biomarkers will prevent many older adults from being excluded from the diagnostic process.
METHODS
In this study, we analyzed selected gene expression profiles, namely, , , , , , , and , in whole blood. The study included 168 subjects divided into five groups: patients hospitalized at the Geriatrics Clinic and Polyclinic with sarcopenia, frailty syndrome, or without those disorders (geriatric control), and non-hospitalized healthy controls (HC) aged 25 to 30 years and over 50 years.
RESULTS
We revealed a lower mRNA level of (p<0.001) in sarcopenic patients compared to the geriatric controls. Furthermore, we detected upregulation of (p=0.003) and (p=0.015) in HC over 50 years old compared to HC aged 25 to 30 years. Interestingly, we observed 2 cluster formations during the gene expression correlation analysis (, , , and , ). We also noted correlations of clinical parameters with mRNA levels in the sarcopenic patients group, such as vitamin D level with (r=0.64, p=0.010), creatine kinase with (r=-0.58, p=0.032) and (r=-0.59, p=0.026), creatinine with (r=0.57, p=0.026), erythrocyte sedimentation rate (ESR) with (r=0.69, p=0.004), and lactate dehydrogenase (LDH) with (r=-0.86, p=0.007). In the frailty syndrome group, we noted a correlation of appendicular skeletal muscle mass (ASMM) with (r=0.59, p=0.026) mRNA level. In the geriatric controls, we observed a correlation of serum iron with mRNA level (r=-0.79, p=0.036).
CONCLUSIONS
Our study revealed as a potential biomarker of sarcopenia. Furthermore, we observed a high expression of epigenetic factors ( and ) in older adults.
背景
表观遗传因素影响炎症衰老以及肌肉减少症和衰弱等老年疾病。开发一种生物标志物或生物标志物组合用于快速简便的诊断很有必要。目前，诊断肌肉减少症需要使用难以获取的设备。生物标志物或生物标志物组合的开发将防止许多老年人被排除在诊断过程之外。
方法
在本研究中，我们分析了全血中选定的基因表达谱，即 、 、 、 、 、 和 。该研究包括168名受试者，分为五组：在老年病诊所和综合诊所住院的患有肌肉减少症、衰弱综合征或无这些疾病的患者（老年对照组），以及25至30岁和50岁以上的非住院健康对照（HC）。
结果
我们发现与老年对照组相比，肌肉减少症患者中 的mRNA水平较低（p<0.001）。此外，我们检测到50岁以上的HC中 （p=0.003）和 （p=0.015）相较于25至30岁的HC上调。有趣的是，在基因表达相关性分析期间我们观察到2个聚类形成（ 、 、 和 、 ）。我们还注意到肌肉减少症患者组中临床参数与mRNA水平的相关性，如维生素D水平与 （r=0.64，p=0.010）、肌酸激酶与 （r=-0.58，p=0.032）和 （r=-0.59，p=0.026）、肌酐与 （r=0.57，p=0.026）、红细胞沉降率（ESR）与 （r=
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