Higher dietary n - 3 PUFA and fiber intake are associated with longer leukocyte telomere length: Evidence from a substitution model analysis in the UK Biobank

Telomere attrition is a biomarker of cellular aging, influenced by lifestyle and dietary exposures. The specific role of macronutrient composition, particularly polyunsaturated fatty acids (PUFAs), in telomere dynamics remains insufficiently explored. We hypothesized that higher intake of specific macronutrients, particularly PUFAs, would be positively associated with leukocyte telomere length (LTL). In this cross-sectional study of 143,553 UK Biobank participants aged 40-69 years, we examined associations between macronutrient intake and standardized LTL (z-LTL), measured as the log-transformed telomere repeat to single-copy gene ratio. Dietary intake was assessed using repeated 24-hour web-based dietary recalls. Multivariable linear regression models were used to estimate associations between macronutrients (% of total energy intake) and z-LTL, adjusting for demographic, lifestyle, and clinical covariates. Effect estimates were translated into age-equivalent changes in LTL. Carbohydrate and total fat intake were positively associated with z-LTL, corresponding to age-related LTL differences of approximately 30-40 days. In energy substitution models, n - 3 PUFA intake showed a stronger positive association with z-LTL than other fats, with adherence to recommended intake associated with differences equivalent to over 2 years (P < .0001) of age-related telomere shortening, whereas no evidence of an association for MUFA was observed. Energy-adjusted fibre intake was associated with an age-related change of LTL equivalent to 1 year (P < .0001). These findings suggest that dietary composition, particularly n - 3 PUFA intake, may be linked with LTL in a manner consistent with healthier cellular aging. Further longitudinal and experimental studies are needed to confirm these associations and explore their implications for dietary guidance.