Molecular underpinnings of physical activity and resilience: A brief overview of the state‐of‐science and research design needs

health promotion, other topics related to stress and health, resilience, stress Regular physical activity/exercise (PA/PE) has proven to have indisputable and powerful effects on maintaining health, preventing disease, extending the healthspan(definition) and lifespan, and may have implications for resilience (Guasch-Ferré et al., 2022;Moore et al., 2016;Piercy & Troiano, 2018;Scully et al., 1998).Although the terms physical activity and exercise are often used interchangeably, PA is considered as any bodily movement that results in energy expenditure.Currently, the COVID-19 pandemic continues to present significant challenges to health and resilience (Torales et al., 2020;Trabelsi et al., 2021).Recent findings show that consistently not meeting PA guidelines during the years preceding the pandemic is a strong risk factor for severe COVID-19 complications, including hospitalisation, admittance to the intensive care unit, and even death (Sallis et al., 2021).The effects of PA on fostering resilience should not be understated, yet significant knowledge and study design gaps remain.As is described in the current Special Issue, the Trans-NIH Resilience Working Group defines resilience as a system's capacity to recover, recover better, adapt, or resist perturbation from a challenge or stressor.Physical activity, as a multidimensional health behaviour that engages a constellation of health-promoting biological pathways, networks, and mechanisms, may facilitate this capacity.From molecular, cellular, and physiological levels of analysis, this brief report elucidates some of the processes and mechanisms involved in association with PA and resilience outcomes in response to physiological, psychosocial, and health-related stressors.Additionally, our study design analysis revealed four critical design features that would be imperative for future investigations to include to be considered a resilience study (see Table 1; Trans-NIH Resilience Working Group, n.d.).First, study designs must include a stressor or a proxy for a stressor to identify the biological responses before and after stressor exposures and their modulation by acute, chronic, or intermittent PA/PE to establish causal associations between PA/PE and resilience outcomes.Second, metrics and measurements should be developed and validated to capture changes that strengthen and empower an individual's psychological, physiological, and molecular capacity to be resilient.Third, there is much heterogeneity in the design and implementation of PA/PE interventions.The field would benefit from identifying the specific components of PA/PE interventions that confer resilience and/or drive molecular/cellular