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

BACKGROUND

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.

PARTICIPANTS AND

METHODS

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.

RESULTS

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.

CONCLUSION

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).