Multidimensional Modeling to Maximize Adaptations to eXercise: The M³AX Trial Rationale and Study Design

Area of Science:

• Gerontology and Exercise Science
• Molecular Biology and Aging
• Personalized Medicine

Background:

• Age-related functional decline affects intrinsic capacity, healthspan, and quality of life.
• Exercise mitigates aging hallmarks, but individual responses (inter-individual response heterogeneity, IRH) vary significantly.
• Mechanisms underlying IRH and effective mitigation strategies remain largely elusive, prompting focused research initiatives.

Purpose of the Study:

• To classify individual responsiveness to combined endurance and resistance training in older adults.
• To interrogate the mechanistic underpinnings of exercise response heterogeneity (IRH).
• To develop and test strategies for boosting exercise responsiveness in older adults.

Main Methods:

• A two-phase Sequential Multiple Assignment Randomized Trial (SMART) design was implemented.
• Phase I involves classifying individual responsiveness and interrogating mechanistic underpinnings.
• Deep in vivo, ex vivo, and molecular phenotyping will be used to establish responsiveness biocircuitry and build predictive models.

Main Results:

• The study is designed to classify individual exercise responsiveness.
• Mechanistic underpinnings of IRH will be investigated using comprehensive phenotyping.
• Predictive models for personalized exercise prescriptions will be developed.

Conclusions:

• Understanding the factors underlying IRH is crucial for optimizing exercise interventions in older adults.
• This research aims to provide a basis for personalized exercise prescriptions tailored to individual responsiveness.
• The findings are expected to enhance the clinical efficacy of exercise training for improving healthspan and quality of life in aging populations.