Correa-Burrows Paulina, Burrows Raquel, Albala Cecilia, Sepúlveda Carlos, Salech Felipe, Troncoso Rodrigo, Bunout Daniel, Gonzalez-Billault Christian
Institute of Nutrition & Food Technology, Universidad de Chile, Santiago, Chile.
Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Chile.
JAMA Netw Open. 2025 Jul 1;8(7):e2520011. doi: 10.1001/jamanetworkopen.2025.20011.
It remains unclear whether obesity accelerates biological aging, potentially leading to early-onset chronic diseases.
To investigate the association between long-term obesity and the expression of biochemical aging markers in younger adults.
DESIGN, SETTING, AND PARTICIPANTS: This multiple-events case-control study, conducted from April 5, 2022, to June 29, 2023, was embedded in the Santiago Longitudinal Study, a prospective Chilean birth cohort of adults aged 28 to 31 years among whom health and nutrition data were collected from September 1992 onward.
Body mass index (BMI) trajectory across the life course, recorded multiple times since birth. Group 1 had healthy BMI across the life course, group 2 had persistent obesity since adolescence, and group 3 had persistent obesity since childhood.
Smoothed BMI trajectories (cubic polynomials) were used to estimate obesity duration. Primary outcomes were DNA methylation-based age and telomere length (TL). Secondary outcomes included levels of aging-related cytokines, growth factors, and adipomyokines.
In the sample of 205 adults (mean [SD] age, 28.9 [0.6] years; 100 females [49%]), 89 (43%) were in group 1, 43 (21%) in group 2, and 73 (36%) in group 3. Mean (SD) obesity duration was 12.9 (4.8) years in group 2 and 26.6 (2.3) years in group 3. Long-term obesity was associated with adulthood expression of biomarkers denoting antagonistic and integrative aging hallmarks, including mean (SD) hs-CRP (1.69 [2.1] vs 3.67 vs 4.24 [2.4] mg/L; P < .001; f = 0.57 [95% CI, 0.44-0.70]) and IL-6 (log, 0.69 [0.5] vs 1.03 [0.4] vs 0.99 [0.4]; P < .001; f = 0.53 [95% CI, 0.41-0.62]), as well as FGF-21, IGF-1, IGF-2, apelin, and irisin. Cohen f coefficient indicated a large effect size for the association of long-term obesity with adulthood expression of these markers.
In this multiple-events case-control study, long-term obesity was associated with the expression of biochemical aging markers in adults aged 28 to 31 years, consistent with epigenetic alterations, telomere attrition, chronic inflammation, impaired nutrient sensing, mitochondrial stress, and compromised intercellular communication. In young adults, chronic health issues may emerge from accelerated biological aging associated with long-term obesity.
肥胖是否会加速生物衰老并可能导致早发性慢性病仍不清楚。
研究年轻成年人中长期肥胖与生化衰老标志物表达之间的关联。
设计、地点和参与者：这项多事件病例对照研究于2022年4月5日至2023年6月29日进行，纳入了圣地亚哥纵向研究，这是一项对智利28至31岁成年人的前瞻性出生队列研究，自1992年9月起收集健康和营养数据。
自出生以来多次记录的整个生命过程中的体重指数（BMI）轨迹。第1组在整个生命过程中BMI正常，第2组自青春期起持续肥胖，第3组自儿童期起持续肥胖。
使用平滑后的BMI轨迹（三次多项式）来估计肥胖持续时间。主要结局是基于DNA甲基化的年龄和端粒长度（TL）。次要结局包括衰老相关细胞因子、生长因子和脂肪肌动蛋白的水平。
在205名成年人样本中（平均[标准差]年龄为28.9[0.6]岁；100名女性[49%]），89人（43%）在第1组，43人（21%）在第2组，73人（36%）在第3组。第2组的平均（标准差）肥胖持续时间为12.9（4.8）年，第3组为26.6（2.3）年。长期肥胖与表示拮抗性和综合性衰老特征的生物标志物在成年期的表达相关，包括平均（标准差）高敏C反应蛋白（1.69[2.1]对3.67对4.24[2.4]mg/L；P < .001；f = 0.57[95%CI，0.44 - 0.70]）和白细胞介素-6（对数，0.69[0.5]对1.03[0.4]对0.99[0.4]；P < .001；f = 0.53[95%CI，0.41 - 0.62]），以及成纤维细胞生长因子-21、胰岛素样生长因子-1、胰岛素样生长因子-2、apelin和鸢尾素。科恩f系数表明长期肥胖与这些标志物在成年期表达之间的关联具有较大效应量。
在这项多事件病例对照研究中，长期肥胖与28至31岁成年人生化衰老标志物的表达相关，这与表观遗传改变、端粒损耗、慢性炎症、营养感知受损、线粒体应激和细胞间通讯受损一致。在年轻成年人中，慢性健康问题可能源于与长期肥胖相关的生物衰老加速。
