DO-HEALTH-BIO-AGE Trial
Description: Background and rationale: Slowing biological aging may be the lever to overcome the public health challenges of an aging society. The most promising key to move this lever is healthy life-style changes, being well-established and modifiable drivers of longevity. Indeed, in large cohort studies and small exploratory trials, increasing physical activity or adherence to an omega-3 rich Mediterranean diet or using vitamin D supplements, slowed biological age acceleration, suggesting that these healthy life-style factors may support a person to be biologically younger in the sense of fitter/healthier than expected. However, these evidence come from either cohort studies or clinical trials with small number of participants and short duration. Evidence from well designed, larger randomized clinical trials with longer duration of follow up to prove such benefits are urgently needed but missing to date. Overall objectives: We aim to close these knowledge gaps by extending the large European DO-HEALTH trial by using Epigenetic Age Acceleration (EAA) as a validated measure of biological age acceleration. Our first aim is to test the effects of vitamin D, omega-3, and a simple home exercise program (SHEP), individually and in combination, on biological aging measured by EAA change (difference between EAA at baseline and three years of follow-up) in community-dwelling adults age 70 and older. Our second aim is to identify personalized optimal intervention or combination of the three interventions on slowing biological aging (negative EAA change between baseline and three years of follow-up), in 12 strata defined by participant’s sex, age, baseline body mass index (BMI), baseline physical activity and baseline blood levels of the nutrients tested. Our third aim is to quantify the economic benefits of slowing biological aging based on EAA change including direct costs related to healthcare utilization and quality-adjusted life years (QALYs). Methods: To achieve our aims, we will take advantage of the trial structure and already collected clinical and health economic data, as well as biobank DNA from the largest European healthy aging trial DO-HEALTH, which recruited and followed 2157 participants from 2012 to 2017. DO-HEALTH was a three-year 2x2x2 factorial design double-blind RCT which enrolled adults age 70 years and older and tested the individual and cumulative benefit of vitamin D 2000 IU/d, omega-3 1 g/d and a 30-minute three times/week SHEP (or sham exercise program) on several clinical outcomes (ClinicalTrials.gov Identifier: NCT01745263). At baseline and year three of the yearly clinical visits, biomaterial was collected for the DO-HEALTH biobank-DNA. Additional follow-up was by in-person phone calls every three months to collect information on new health events and health care utilization. For the DO-HEALTH-BIO-AGE-Trial, we will utilize the DO-HEALTH biobank-DNA collected at baseline and year three to measure EAA change based on two DNA methylation patterns (Horvath and PhenoAge epigenetic clocks), in 1642 DO-HEALTH participants with DNA-biobank samples and consent for both time points. Expected results and impact: The prospects of this project are several. First, DO-HEALTH-BIO-AGE will be the first larger and longer term (three-year follow-up) clinical trial to clarify the role of three public health interventions that showed promise in several smaller trials in slowing biological aging. Second, the trial design will allow us to derive personalized treatment benefits based on individual and combined effects of the interventions overall and in key subgroups of older adults. Third, the study has the potential to support broad health policy efforts by providing cost-effectiveness of slowing biological aging. Finally, the innovative approach of using the DO-HEALTH trial structure & biobank DNA for the DO-HEALTH-BIO-AGE-trial allows us to provide primary results of a large three-year clinical trial on slowing biological aging in a very efficient time window of 28 months for the main RCT-findings, thereby advancing public health rapidly.
Amount: CHF 719,000
Funding type: research
Funder scheme: Project funding
Start date: 2021-11-01
End date: 2025-01-31
Investigator: Bischoff-Ferrari, Heike A.
Institution: University of Zurich – ZH
Funded outputs count: 2
Funder award ID: 204452
OpenAlex ID: G2465426743