Chronic inflammation represents one of the most consistent biologic features of aging. However, the precise etiology of persistent low-grade increases in inflammation remains unclear. Recent evidence suggests that the gut microbiome may play a key role in age-related inflammation. Indeed, several studies have indicated that older adults display an altered composition of the gut microbiota, and early evidence indicates that this dysbiosis is associated with the presence of several key circulating inflammatory analytes. The present review summarizes knowledge on age-related inflammation and discusses how potential relationships with gut dysbiosis may lead to novel treatment strategies in the future. “The pattern of disease is an expression of the response of man to his total environment (physical, biological, and social); this response is, therefore, determined by anything that affects man himself or his environment.” – Rene Dubos, 1961

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood^1–3. Here, the Molecular Transducers of Physical Activity Consortium⁴ profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository (https://motrpac-data.org/).

Design, six apparently healthy young adults (22 ± 1 yr) performed 120 unilateral knee extensions at 40% of 1 repetition maximum with and without BFR (CNTRL). Near-infrared spectroscopy was used to measure oxygenation of the vastus lateralis during exercise. Serum and muscle expression of Post–Resistance vascular endothelial growth factor (VEGF) were determined preexercise, 4 h postexercise, and 24 h postexercise. Transcript (mRNA) expression of VEGF and other angiogenic genes was also determined. Results BFR increased muscle hemoglobin (Hb) concentrations during exercise (14.4 ± 1.6 vs. 0.9 ± 1.6, P = 0.002), driven largely by an increase in deoxygenated Hb (11.0 ± 2.5 vs. 0.5 ± 1.1, P = 0.030). BFR also increased (P < 0.05) transcript expression of VEGF, VEGF-R2, hypoxia-inducible factor 1 alpha, inducible nitric oxide synthase (NOS), and neuronal NOS. The most dramatic change in response to BFR was an increase in VEGF mRNA at 4 h postexercise (4.1 ± 0.6 vs. 0.6 ± 0.2-fold change, P = 0.028). Compared with control, transcript expression of endothelial NOS, serum VEGF, or muscle protein expression of VEGF was not altered in response to BFR (P > 0.05). Conclusion Acute BFR increases postexercise expression of mRNA related to skeletal muscle angiogenesis, plausibly in response to changes in muscle Hb concentrations....