Long-Term Obesity and Biological Aging in Young Adults

Importance It remains unclear whether obesity accelerates biological aging, potentially leading to early-onset chronic diseases. Objective 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. Exposure 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. Main Outcomes and Measures 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. Results 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. Conclusions and Relevance 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.