Long-term obesity was associated with markers of accelerated biological aging in adults aged 28-31 years, according to a multiple-events, case-control study published in JAMA Network Open.

Investigators Paulina Correa-Burrows, PhD, et al., separated 205 Chilean adults (mean age, 29 years; 49% women) from the Santiago Longitudinal Study into three groups: healthy BMI across life course (Group 1; n=89; 43%), persistent obesity since adolescence (Group 2; n=43; 21%; mean obesity duration, 12.9 years) and persistent obesity since childhood (Group 3; n=73; 36%; mean obesity duration, 26.6 years).

Participants in both persistent obesity groups had higher waist circumference, systolic blood pressure, insulin level, HOMA-IR and HOMA-β, as well as reduced HDL-C. Groups 2 and 3 also had a median Hamaguchi score of 4, indicating higher likelihood of metabolic-dysfunction-associated steatotic liver disease.

The two primary outcomes were leukocyte telomere length (LTL) and epigenetic age, determined using DNA from a 25-mL blood sample collected during an assessment and estimated with both Horvath and GrimAge DNA-methylation-based age clocks.

Results showed that DNA-methylation-based age as calculated by the Horvath clock decreased in Group 1 (–1.4%) and increased in Groups 2 and 3 (15.2% and 16.4%, respectively). Similar patterns presented when using the GrimAge model (–10.2% vs. 7.7% vs. 10.7%). Investigators note that for some participants, the difference between chronological and biological aging was as much as 48%. Mean LTL was 8.01 kb in Group 1, 7.46 kb in Group 2 and 7.42 in Group 3.

Investigators also recorded an increase in Groups 2 and 3 in biomarkers for chronic inflammation, impaired nutrient sensing, mitochondrial stress and compromised intercellular communication. Compared to Group 1, Groups 2 and 3 had higher mean high sensitivity-CRP (1.69 vs. 3.67 vs. 4.24 mg/L; p<0.001) and IL-6 (log, 0.69 vs. 1.03 vs. 0.99; p<0.001) levels, as well as higher FGF-21, apelin and irisin concentrations.

Statistical analysis did not find significant difference between these mean values in Groups 2 and 3, indicating a similar effect regardless of obesity onset. This equated to an increase in biological age of two to five years in groups with persistent obesity.

"With an estimated [one] billion people expected to have obesity by 2030, we are approaching a future where the global population may be physiologically older than current sociodemographic data suggest, jeopardizing efforts for healthy, functional and successful aging," warn the authors.

"The results speak for themselves," writes Antonello Lorenzini, PhD, in an accompanying editorial comment, noting that the findings could be a vital element for future anti-obesity educational campaigns. "It is reasonable now to hypothesize that the excess calories that precede and accompany obesity, or obesity itself as a state of modified hormonal balance, or a combination of both these aspects, may accelerate the aging process."