OVERVIEW:
Exercise is fundamental for good health, whereas physical inactivity underpins many chronic diseases of modern society. It is well appreciated that regular exercise improves metabolism and the metabolic phenotype in a number of tissues.
The phenotypic alterations observed in skeletal muscle are partly mediated by transcriptional responses that occur following each individual bout of exercise. This adaptive response increases oxidative capacity and influences the function of myokines and extracellular vesicles that signal to other tissues.
Our understanding of the epigenetic and transcriptional mechanisms that mediate the skeletal muscle gene expression response to exercise as well as of their upstream signalling pathways has advanced substantially in the past 10 years.
With this knowledge also comes the opportunity to design new therapeutic strategies based on the biology of exercise for a variety of chronic conditions where regular exercise might be a challenge.
This Review provides an overview of the beneficial adaptive responses to exercise and details the molecular mechanisms involved. The possibility of designing therapeutic interventions based on these molecular mechanisms is addressed, using relevant examples that have exploited this approach.
Key points
Exercise is effective in the primary prevention of 35 chronic diseases.
- Heart disease
- Stroke
- High blood pressure
- Type 2 diabetes
- Obesity
- Osteoporosis
- Arthritis
- Chronic obstructive pulmonary disease (COPD)
- Asthma
- Certain cancers (e.g., breast, colon)
- Depression
- Anxiety
- Dementia
- Alzheimer’s disease
- Metabolic syndrome
- High cholesterol
- Gallbladder disease
- Non-alcoholic fatty liver disease
- Sleep apnea
- Chronic back pain
- Chronic neck pain
- Fibromyalgia
- Irritable bowel syndrome (IBS)
- Chronic kidney disease
- Peripheral artery disease
- Varicose veins
- Gout
- Polycystic ovary syndrome (PCOS)
- Erectile dysfunction
- Chronic fatigue syndrome
- Migraine
- Psoriasis
- Eczema
- Multiple sclerosis
- Inflammatory bowel disease (IBD)
The adaptive response to exercise, which is mediated in part by transcriptional alterations in metabolic and other genes, is an important contributor to these health benefits.
Identifying the mechanisms that mediate the exercise adaptive response could uncover molecular targets to guide the design of new medicines to better treat chronic diseases.
A number of signalling, epigenetic and transcriptional molecules identified as contributing to the exercise adaptive response have been targeted pharmacologically to deliver health benefits in proof-of-concept studies.
A further understanding of the complexities of the molecular responses to exercise will provide new opportunities to engage these mechanisms therapeutically.
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