PDF(Pubmed)
Abstract：
Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined.
We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight).
Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02).
This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging.
ClinicalTrials.gov, NCT03020186.
We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight).
Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02).
This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging.
ClinicalTrials.gov, NCT03020186.
摘要：
背景：表观遗传年龄是基于DNA甲基化的生物年龄的估计；其与实际年龄的差异值得进一步研究。我们最近报道，更多的多酚摄入量有利于异位脂肪，大脑功能,和肠道微生物群概况，与升高的尿液多酚相对应。富含多酚的膳食干预对生物衰老的影响尚待确定。
方法：我们计算了不同世代的不同生物衰老表观遗传时钟（Horvath2013，Hannum2013，Li2018，Horvath皮肤和血液2018，PhenoAge2018，PCGrimAge2022），他们相应的年龄和内在年龄加速度，和DunedinPACE,全部基于256名腹部肥胖或血脂异常参与者的DNA甲基化（IlluminaEPIC阵列；预先指定的次要结果），在18个月DIRECTPLUS随机对照试验之前和之后。分配了三种干预措施：健康饮食指南，地中海（MED）饮食，富含多酚，低红/加工肉绿色MED饮食。两个MED组每天食用28克核桃(+440mg/天多酚)。Green-MED组食用绿茶（3-4杯/天）和Mankai（Wolfiaglobosa菌株）500毫升绿色奶昔（800毫克/天的多酚）。通过问卷调查和尿液多酚代谢组学（高效液相色谱四极杆飞行时间）评估对Green-MED饮食的依从性。
结果：基线年龄（51.3±10.6岁）与所有甲基化年龄（mAge）时钟显着相关，相关性范围为0.83至0.95；所有p<2.2e-16。虽然所有干预措施在mAge时钟之间的变化方面没有差异，较高的Green-Med饮食依从性与较低的18个月相对变化相关(即，更大的mAge衰减）在Li和HannummAge中（分别为β=-0.41，p=0.004和β=-0.38，p=0.03；多变量模型）。更大的LimAge衰减(多变量模型根据年龄调整，性别,基线mAge,和体重减轻）主要受到Mankai（β=-1.8;p=0.061）和绿茶（β=-1.57;p=0.0016）的较高摄入量的影响，并且与升高的尿液多酚相对应：羟基酪醇，酪醇,和尿石素C（全部p<0.05）和尿石素A（p=0.08），在绿色植物中非常常见。总的来说,在干预结束时,接受任何一种MED式饮食的参与者在观察到的和预期的LimAge之间有约8.9个月的有利差异(p=0.02).
结论：这项研究表明，MED和绿色MED饮食增加多酚摄入量，比如绿茶和曼凯，与生物衰老成反比。据我们所知,这是第一个表明多酚摄入之间潜在联系的临床试验，尿多酚，和生物老化。
背景：ClinicalTrials.gov，NCT03020186。
方法：我们计算了不同世代的不同生物衰老表观遗传时钟（Horvath2013，Hannum2013，Li2018，Horvath皮肤和血液2018，PhenoAge2018，PCGrimAge2022），他们相应的年龄和内在年龄加速度，和DunedinPACE,全部基于256名腹部肥胖或血脂异常参与者的DNA甲基化（IlluminaEPIC阵列；预先指定的次要结果），在18个月DIRECTPLUS随机对照试验之前和之后。分配了三种干预措施：健康饮食指南，地中海（MED）饮食，富含多酚，低红/加工肉绿色MED饮食。两个MED组每天食用28克核桃(+440mg/天多酚)。Green-MED组食用绿茶（3-4杯/天）和Mankai（Wolfiaglobosa菌株）500毫升绿色奶昔（800毫克/天的多酚）。通过问卷调查和尿液多酚代谢组学（高效液相色谱四极杆飞行时间）评估对Green-MED饮食的依从性。
结果：基线年龄（51.3±10.6岁）与所有甲基化年龄（mAge）时钟显着相关，相关性范围为0.83至0.95；所有p<2.2e-16。虽然所有干预措施在mAge时钟之间的变化方面没有差异，较高的Green-Med饮食依从性与较低的18个月相对变化相关(即，更大的mAge衰减）在Li和HannummAge中（分别为β=-0.41，p=0.004和β=-0.38，p=0.03；多变量模型）。更大的LimAge衰减(多变量模型根据年龄调整，性别,基线mAge,和体重减轻）主要受到Mankai（β=-1.8;p=0.061）和绿茶（β=-1.57;p=0.0016）的较高摄入量的影响，并且与升高的尿液多酚相对应：羟基酪醇，酪醇,和尿石素C（全部p<0.05）和尿石素A（p=0.08），在绿色植物中非常常见。总的来说,在干预结束时,接受任何一种MED式饮食的参与者在观察到的和预期的LimAge之间有约8.9个月的有利差异(p=0.02).
结论：这项研究表明，MED和绿色MED饮食增加多酚摄入量，比如绿茶和曼凯，与生物衰老成反比。据我们所知,这是第一个表明多酚摄入之间潜在联系的临床试验，尿多酚，和生物老化。
背景：ClinicalTrials.gov，NCT03020186。
