The American Journal of Clinical Nutrition

The American Journal of Clinical Nutrition

Report of a Meeting

Muscle movement and metabolism: exercise and skeletal muscle as mediators of health-a report from the twenty-sixth Annual Harvard Nutrition Obesity Symposium, twenty twenty-five

ABSTRACT

Skeletal muscle is a crucial facilitator of many of the effects of exercise on metabolic health. Intrinsic myocellular mechanisms, exercise-induced myokine secretion, and crosstalk between multiple organ systems contribute to the maintenance of energy homeostasis, cardiovascular health, strength, cognition, and quality of life. Investigating the molecular underpinnings of the skeletal muscle response to exercise from multiple perspectives, including the genetic, physiological, and environmental factors leading to metabolic dysfunction, has advanced our understanding of disease risk and helped identify avenues for the prevention and treatment of metabolic disorders and chronic diseases. The National Institutes of Health-funded Boston Area Nutrition Obesity Research Center, in partnership with the Harvard Medical School Division of Nutrition, hosted its twenty-sixth Annual Symposium, "Muscle Movement and Metabolism: Exercise and Skeletal Muscle as Mediators of Health," in June of twenty twenty-five. Speakers presented novel research and unique perspectives on exercise and skeletal muscle as key determinants of health. This manuscript synthesizes the symposium's major themes: one) physiological and molecular mechanisms of exercise, two) clinical implications of physical inactivity and reduced muscle function, and three) individual variability and personalized medicine. By bridging mechanistic and clinical insights with principles of personalized medicine, the symposium provided key insights into the current landscape of treatments for metabolic diseases and evidence-based strategies for disease prevention.

Introduction

The interplay between physical activity, skeletal muscle, and metabolism has profound effects on health and longevity. The Centers for Disease Control and Prevention defined physical activity as any bodily movement that produces energy expenditure, whereas exercise is a subtype of activity that is planned, structured, and repetitive. Indeed, engaging in regular physical activity and exercise is known to protect against a broad range of health concerns across the lifespan, including cardiovascular disease, stroke, cancers, diabetes, and age-related cognitive decline. Physical activity in childhood is associated with improved cognitive functioning, academic performance, and mental health, early childhood exercise is also linked with improvements in cardiovascular risk factors, bone development, and body fat and mass measures. In older adults, physical activity reduces the risk of chronic age-related conditions and improves quality of life, mental and physical health, and cognition. The World Health Organization consistently recommends limiting sedentary behavior and maintaining physical activity based on robust evidence that exercise reduces the risk of adverse health outcomes while controlling for other risk factors.

With the increasing life expectancy of humans, scientific investigations have focused on identifying strategies to optimize healthful years, termed the "healthspan." Physical activity typically declines with age due to environmental factors and chronic disease onset, which highlights the clinical relevance of determining how exercise-induced enhancements in skeletal muscle and metabolism can protect against the decline of health. Physical activity and exercise play a key role in improving the healthspan through their multisystem effects on skeletal muscle mass, glucose metabolism, and cardiovascular health. The function of skeletal muscle has been compared with that of an endocrine organ. As such, in-depth characterizations of the cytokines and other immunomodulating peptides produced and released by muscle fibers demonstrate the far-reaching effects of muscle-contracting exercise on other organ systems. These endocrine-like processes via muscle-derived myokines are thought to induce metabolic adaptations with impacts across multiple organ systems, ultimately leading to lifelong benefits in health.

Novel technologies have allowed for in-depth longitudinal monitoring of health and lifestyle data in large cohorts of participants. The ability to integrate longitudinal data incorporating lifestyle factors and physiological outcomes provides exciting possibilities for this field, results of which have elucidated how exercise, nutrition, environmental exposures, and pathogens influence health over time. This approach applies the principles of personalized care and precision medicine to the study of exercise science. The twenty twenty-five Harvard Nutrition and Obesity Research Center Symposium featured experts who presented topics broad in scope, but united under this framework. Presenters reviewed the physiological and molecular mechanisms of physical activity and exercise, particularly in their regulation of glucose metabolism and the central role of skeletal muscle in metabolic adaptation. After reviewing foundational literature and emerging studies, presenters discussed clinical applications, potential benefits, and practical considerations of exercise intervention in distinct populations and future directions for the field.