Rigamonti Antonello E, Bollati Valentina, Favero Chiara, Albetti Benedetta, Caroli Diana, Abbruzzese Laura, Cella Silvano G, Sartorio Alessandro
Department of Clinical Sciences and Community Health, University of Milan, 20129 Milan, Italy.
EPIGET Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.
J Clin Med. 2022 Aug 10;11(16):4677. doi: 10.3390/jcm11164677.
Obesity and aging share common molecular and cellular mechanisms underlying the pathophysiology of cardiovascular diseases (CVD), which occur frequently in both conditions. DNA methylation (DNAm) age, a biomarker of the epigenetic clock, has been proposed as a more accurate predictor of biological aging than chronological age. A positive difference between an individual’s chronological age and DNAm age is referred to as epigenetic age acceleration. The objective of the present study was to evaluate the effects of a 3-week in-hospital body weight reduction program (BWRP) on the epigenetic age acceleration, as well as on other cardiometabolic outcomes, in a cohort of 72 obese adults (F/M: 43/29; (chronological) age: 51.5 ± 14.5 yrs; BMI: 46.5 ± 6.3 kg/m2). At the end of the BWRP, when considering the entire population, BMI decreased, and changes in body composition were observed. The BWRP also produced beneficial metabolic effects as demonstrated by decreases in glucose, insulin, HOMA-IR, total cholesterol, and LDL cholesterol. A post-BWRP improvement in cardiovascular function was also evident (i.e., decreases in systolic and diastolic blood pressures and heart rate). The BWRP reduced some markers of systemic inflammation, particularly C-reactive protein (CRP). Finally, vascular age (VA) and Framingham risk score (FRS) were reduced after the BWRP. When considering the entire population, DNAm age and epigenetic age acceleration did not differ after the BWRP. However, when subdividing the population into two groups based on each subject’s epigenetic age acceleration (i.e., ≤0 yrs or >0 yrs), the BWRP reduced the epigenetic age acceleration only in obese subjects with a value > 0 yrs (thus biologically older than expected). Among all the single demographic, lifestyle, biochemical, and clinical characteristics investigated, only some markers of systemic inflammation, such as CRP, were associated with the epigenetic age acceleration. Moreover, chronological age was correlated with DNAm age and VA; finally, there was a correlation between DNAm age and VA. In conclusion, a 3-week BWRP is capable of reducing the epigenetic age acceleration in obese adults, being the BWRP-induced rejuvenation evident in subjects with an epigenetic age acceleration > 0 yrs. Based on the BWRP-induced decrease in CRP levels, chronic systemic inflammation seems to play a role in mediating obesity-related epigenetic remodeling and biological aging. Thus, due to the strong association of CVD risk with the epigenetic clock and morbidity/mortality, any effort should be made to reduce the low-grade chronic inflammatory state in obesity.
肥胖和衰老在心血管疾病（CVD）的病理生理学中有着共同的分子和细胞机制，这两种情况中CVD都很常见。DNA甲基化（DNAm）年龄是表观遗传时钟的一个生物标志物，已被认为是比实际年龄更准确的生物衰老预测指标。个体的实际年龄与DNAm年龄之间的正差异被称为表观遗传年龄加速。本研究的目的是评估一项为期3周的住院体重减轻计划（BWRP）对72名肥胖成年人（男/女：43/29；实际年龄：51.5±14.5岁；BMI：46.5±6.3kg/m²）队列中表观遗传年龄加速以及其他心脏代谢指标的影响。在BWRP结束时，考虑整个人群，BMI下降，身体成分也有变化。BWRP还产生了有益的代谢作用，表现为血糖、胰岛素、HOMA-IR、总胆固醇和低密度脂蛋白胆固醇降低。BWRP后心血管功能也有明显改善（即收缩压、舒张压和心率降低）。BWRP降低了一些全身炎症标志物，特别是C反应蛋白（CRP）。最后，BWRP后血管年龄（VA）和弗雷明汉风险评分（FRS）降低。考虑整个人群时，BWRP后DNAm年龄和表观遗传年龄加速没有差异。然而，当根据每个受试者的表观遗传年龄加速（即≤0岁或>0岁）将人群分为两组时，BWRP仅在表观遗传年龄加速值>0岁（因此生物学年龄比预期大）的肥胖受试者中降低了表观遗传年龄加速。在所有调查的单一人口统计学、生活方式、生化和临床特征中，只有一些全身炎症标志物，如CRP，与表观遗传年龄加速有关。此外，实际年龄与DNAm年龄和VA相关；最后，DNAm年龄与VA之间存在相关性。总之，为期3周的BWRP能够降低肥胖成年人的表观遗传年龄加速，在表观遗传年龄加速>0岁的受试者中BWRP诱导的年轻化很明显。基于BWRP导致的CRP水平降低，慢性全身炎症似乎在介导肥胖相关的表观遗传重塑和生物衰老中起作用。因此，由于CVD风险与表观遗传时钟以及发病率/死亡率密切相关，应尽一切努力降低肥胖中的低度慢性炎症状态。
