Chitta Pitaksin, Pratumvinit Busadee, Kaewboonruang Witchayaporn, Dawangpa Atchara, Khamrangsee Saliltip, Assantachai Prasert, Sutiwisesak Rujapope, Wongloet Wongsathit, Tencomnao Tewin, Sae-Lee Chanachai
Research Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Nutr Metab (Lond). 2025 Sep 2;22(1):103. doi: 10.1186/s12986-025-01004-0.
Frailty syndrome poses significant challenges in older populations. Understanding the genetic and biochemical factors associated with frailty is essential for effective management strategies.
In this study, Thai older adults (≥ 60 years, n = 170) were assessed for physical parameters, levels of B vitamins, creatinine, and homocysteine. The polymorphisms of methylenetetrahydrofolate reductase (MTHFR) (677 C > T) and Transcobalamin II (TCN2) 776G > C were identified. Global DNA methylation (global DNAm) was assessed using a colorimetric assay.
Participants were categorised into robust (n = 61), pre-frail (n = 62), and frail (n = 47) groups by Fried criteria and Kihon checklist. The physical parameters, including chair stand, functional reach, gait speed, and handgrip strength, showed highly significant differences among the groups (p < 0.01). Significant differences in folate and vitamin B concentrations were observed between MTHFR and TCN2 genotypes, respectively. In addition, global DNAm levels were significantly lower in pre-frail individuals, particularly among those carrying the MTHFR C677T genotype, compared to both robust and frail groups. Notably, lower global DNAm was associated with a higher likelihood of being classified as pre-frail rather than frail, and a lower likelihood of being pre-frail compared to robust individuals. Moreover, correlation analyses revealed significant associations among physical parameters, clinical characteristics, and global DNAm.
This study demonstrated the interplay between genetic variants, micronutrient status, and epigenetic modifications in the context of frailty among older adults. These findings highlight the potential of epigenetic and metabolic markers in identifying early frailty, though longitudinal and mechanistic studies are needed to further clarify causal pathways.
This study was duly registered with the Thai Clinical Trial under the identifier TCTR20240626002 (date of registration: 21/06/2024).
衰弱综合征给老年人群带来了重大挑战。了解与衰弱相关的遗传和生化因素对于有效的管理策略至关重要。
在本研究中，对泰国老年人（≥60岁，n = 170）进行了身体参数、B族维生素水平、肌酐和同型半胱氨酸的评估。确定了亚甲基四氢叶酸还原酶（MTHFR）（677C>T）和转钴胺素II（TCN2）776G>C的多态性。使用比色法评估全基因组DNA甲基化（global DNAm）。
根据Fried标准和Kihon检查表，参与者被分为健康组（n = 61）、衰弱前期组（n = 62）和衰弱组（n = 47）。身体参数，包括从椅子上站起、功能性伸展、步速和握力，在各组之间显示出高度显著差异（p < 0.01）。分别在MTHFR和TCN2基因型之间观察到叶酸和维生素B浓度的显著差异。此外，与健康组和衰弱组相比，衰弱前期个体的全基因组DNA甲基化水平显著较低，特别是那些携带MTHFR C677T基因型的个体。值得注意的是，较低的全基因组DNA甲基化与被归类为衰弱前期而非衰弱的可能性较高相关，与健康个体相比，被归类为衰弱前期的可能性较低。此外，相关性分析揭示了身体参数、临床特征和全基因组DNA甲基化之间的显著关联。
本研究证明了老年衰弱背景下遗传变异、微量营养素状态和表观遗传修饰之间的相互作用。这些发现突出了表观遗传和代谢标志物在识别早期衰弱方面的潜力，不过需要纵向和机制研究来进一步阐明因果途径。
本研究已在泰国临床试验中正式注册，标识符为TCTR20240626002（注册日期：2024年6月21日）。
