Effect of a Multifactorial Weight Loss Intervention on HDL Cholesterol Efflux Capacity and Immunosenescence: A Randomized Controlled Trial

Objective: Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. Method: CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. Results: Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (-3.32% +/- 12.54% and -6.74% +/- 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. Conclusions: A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.