Zachary A Graham, Matthew P Bubak, Christiana J Raymond-Pope, Gary R Cutter, Jeremy S McAdam, S Craig Tuggle, Jacob A Siedlik, Luis G O de Sousa, Ed J Chappe, Kana Meece, Amritpal Kaur, Benny S R Ruiz, Sophia C Bamman, Katherine M Vanselow, Trevor W Perry, Jorge S Acosta-Arreguin, Natalie J Bohmke, Greg J Addison, J Michelle Bowers, Rachel L Wright, Lena D Fuentes, Jennifer E Smith, Karyn A Esser, Benjamin F Miller, Sue C Bodine, Marcas M Bamman
{"title":"Multidimensional Modeling to Maximize Adaptations to eXercise: The M<sup>3</sup>AX Trial Rationale and Study Design.","authors":"Zachary A Graham, Matthew P Bubak, Christiana J Raymond-Pope, Gary R Cutter, Jeremy S McAdam, S Craig Tuggle, Jacob A Siedlik, Luis G O de Sousa, Ed J Chappe, Kana Meece, Amritpal Kaur, Benny S R Ruiz, Sophia C Bamman, Katherine M Vanselow, Trevor W Perry, Jorge S Acosta-Arreguin, Natalie J Bohmke, Greg J Addison, J Michelle Bowers, Rachel L Wright, Lena D Fuentes, Jennifer E Smith, Karyn A Esser, Benjamin F Miller, Sue C Bodine, Marcas M Bamman","doi":"10.1152/japplphysiol.00486.2025","DOIUrl":null,"url":null,"abstract":"<p><p>Age-related functional declines are thought to be caused by hallmark biological processes that manifest in physical, mental, and metabolic impairments compromising intrinsic capacity, healthspan and quality-of-life. Exercise is a multipotent treatment with promise to mitigate most aging hallmarks, but there is substantial variability in individual exercise responsiveness. This inter-individual response heterogeneity (IRH) was first extensively interrogated by Bouchard and colleagues in the context of endurance training. Our group has interrogated IRH in response to resistance training and combined training, and we have conducted trials in older adults examining dose titration and adjuvant treatments in attempts to boost response rates. Despite the work of many groups, the mechanisms underpinning IRH and effective mitigation strategies largely remain elusive. The National Institute on Aging (NIA) hosted a focused workshop in 2022 titled \"Understanding heterogeneity of responses to, and optimizing clinical efficacy of, exercise training in old adults\". This workshop spurred a dedicated NIA request for applications (RFA) with the major goal \"to better understand factors underlying response variability to exercise training in older adults.\" We developed a two-phase Sequential Multiple Assignment Randomized Trial (SMART) in response to the RFA that will allow us to classify individual responsiveness to combined endurance and resistance training and interrogate potential mechanistic underpinnings (Phase I), followed by an approach to boost responsiveness (Phase II). Using deep in vivo, ex vivo, and molecular phenotyping, we will establish multidimensional biocircuitry of responsiveness and build predictive models, providing a basis for personalized exercise prescriptions.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of applied physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/japplphysiol.00486.2025","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Age-related functional declines are thought to be caused by hallmark biological processes that manifest in physical, mental, and metabolic impairments compromising intrinsic capacity, healthspan and quality-of-life. Exercise is a multipotent treatment with promise to mitigate most aging hallmarks, but there is substantial variability in individual exercise responsiveness. This inter-individual response heterogeneity (IRH) was first extensively interrogated by Bouchard and colleagues in the context of endurance training. Our group has interrogated IRH in response to resistance training and combined training, and we have conducted trials in older adults examining dose titration and adjuvant treatments in attempts to boost response rates. Despite the work of many groups, the mechanisms underpinning IRH and effective mitigation strategies largely remain elusive. The National Institute on Aging (NIA) hosted a focused workshop in 2022 titled "Understanding heterogeneity of responses to, and optimizing clinical efficacy of, exercise training in old adults". This workshop spurred a dedicated NIA request for applications (RFA) with the major goal "to better understand factors underlying response variability to exercise training in older adults." We developed a two-phase Sequential Multiple Assignment Randomized Trial (SMART) in response to the RFA that will allow us to classify individual responsiveness to combined endurance and resistance training and interrogate potential mechanistic underpinnings (Phase I), followed by an approach to boost responsiveness (Phase II). Using deep in vivo, ex vivo, and molecular phenotyping, we will establish multidimensional biocircuitry of responsiveness and build predictive models, providing a basis for personalized exercise prescriptions.
期刊介绍:
The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.