Structured lifestyle modification and biological aging: effects on PhenoAge, sclerostin, and GDF-15 in arab adults...

Lifestyle modification programs (LMP) such as diabetes prevention programs may influence phenotypic aging trajectories, but evidence in Middle Eastern populations remains limited. This study examined the effects of a structured LMP on phenotypic age (PhenoAge) as the primary endpoint and circulating sclerostin (SOST) and growth differentiation factor-15 (GDF-15) as secondary endpoints in a cohort of Arab adults with prediabetes.

In this randomized clinical trial (RCT), a total of 181 adults (130 males, 51 females; mean age 50.8 ± 10.9 years, body mass index, BMI 30.0 ± 4.8 kg/m²) were enrolled. Participants were allocated to either a structured LMP or Control Group (CG) and followed for 6 months. The LMP group was requested to reduce weight by 5%, moderate exercise (150 min/week), reduce fat intake (30%) and increase fiber intake (15g/1 kcal). CG was given brochure. PhenoAge was calculated and assessed alongside anthropometrics, blood biomarkers (HbA1c, fasting glucose, albumin, creatinine, GDF15, SOST), and dietary parameters at baseline and after 6 months.

Compared with the CG, participants in the lifestyle modification program (LMP) showed a significant reduction in PhenoAge (-4.9 vs. +1.3 years; between-group p < 0.001). Significant between-group improvements were also observed in weight (-5.7 kg), BMI (-2.0 kg/m²), waist circumference (-6.3 cm), and HbA1c (-0.4%; all p < 0.001). Neither GDF-15 nor SOST demonstrated a significant intervention-specific effect.

A structured lifestyle intervention significantly improved PhenoAge, accompanied by improvements in metabolic parameters in Arab adults with prediabetes. Changes in GDF-15 and SOST appeared time-dependent rather than intervention-specific. These findings support lifestyle modification as a potential strategy to slow a composite clinical measure of biological aging. ClinicalTrial Registration (NCT06440681).