Picture How Exercise Sustains Health

Exercise just may be that "magic pill" everyone is looking for!

Healthy Highlights

• Regular exercise confers multiple health benefits and better survival.
• Regular moderate-intensity of exercise sustains the major hallmarks of health.
• The health benefits of exercise lies in the remarkable integrative adaptation of multiple tissues and organs.
• Exercise appears as a protective strategy to maintain health in response to stress.
• Regular exercise is considered a non-pharmacological polypill for patients with certain comorbidities.

Summary of the main regulatory mechanisms by which exercise sustains health

Exercise impacts the major hallmarks of health, including the integrity of barriers, containment of local perturbations, recycling and turnover, integration of circuitries, rhythmic oscillations, homeostatic resilience, hormetic regulation, as well as repair and regeneration.

Effects of exercise on the integrity of barriers and the underlying mechanisms

The biological changes of barriers through which exercise sustains health. FABPpm = plasma membrane fatty acid-binding protein; FAT = fatty acid translocase; HMGB1 = high mobility group box 1; IL-15 = interleukin-15; Mst1 = mammalian sterile 20-like kinase 1; NF-κB = nuclear factor-kappa B; NPC = nuclear pore complex; PECAM-1 = platelet and endothelial cell adhesion molecule 1; REDD1 = regulated in development and DNA damage 1; TLR4 = toll-like receptor 4.

Benefits of exercise on the maintenance of local homeostasis and the involved mechanisms

Regular exercise at moderate intensity generally contributes to the maintenance of systemic homeostasis. ACE2 = angiotensin-converting enzyme 2; IFNγ = interferon-γ; IL = interleukin; miR = microRNA; NK = natural killer; TMPRSS2 = transmembrane protease serine 2; TNF-α = tumor necrosis factor-α; WBC = white blood cell counts.

Exercise has systemic effects

Exercise leads to systemic effects by evoking the coordinated and integrated adaptation of multiple organ systems. Exercise results in the secretion of myokines, adipokines (e.g., TGFβ, leptin), and hepatokines as well as by-products of gut microbiota (e.g., SCFA) that have key roles in interorgan communication and, thus, mediate many of the beneficial effects of exercise. 5-HT = serotonin; FGF21 = fibroblast growth factor-21; GDF15 = growth differentiation factor-15; HSP72 = heat shock protein 72; SCFA = short-chain fatty acids; SIRT1 = sirtuin 1; TGFβ = transforming growth factor-β.

Exercise-associated beneficial adaptations in response to stress

Exercise confers multiple health benefits via different strategies, including improving resilience, hormetic regulation, and modulating the process of repair and regeneration in response to damage. ER = endoplasmic reticulum; UPR^mt = mitochondrial unfolded protein response.

Regular exercise confers multiple health benefits and better survival

The adaptations in multiple tissues and organ systems contribute to the maintenance of whole-body health. AMPK = adenosine monophosphate–activated protein kinase; BDNF = brain-derived neurotrophic factor; CaMK = calcium/calmodulin-dependent protein kinase; GPx = glutathione peroxidase; IGF1 = insulin-like growth factor 1; MAPK = mitogen-activated protein kinase; NGF = nerve growth factor; NK cells = natural killer cells; NO = nitric oxide; PGC1α = peroxisome-proliferator-activated receptor coactivator 1α; SIRTs = sirtuins; SOD = superoxide dismutase; VEGF = vascular endothelial growth factor; VEGFA = vascular endothelial growth factor A; VEGFR3 = vascular endothelial growth factor receptor 3.

Optimal Takeaways

• The beneficial effects of exercise have been well-documented for a range of improved metabolic and cardiorespiratory fitness-related outcomes.
• Regular exercise is essentially considered a non-pharmacological polypill for patients with certain comorbidities.
• Therapeutic exercise can be adopted to prevent, manage, and treat diseases such as obesity, type 2 diabetes, cardiovascular disease, aging-related muscle atrophy, and certain cancers.
• However, caution should be taken when interpreting these discoveries, as exercise protocols may vary across studies.

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