Immunometabolism and Covid-19: Could Lifelong Exercise Training Have a Protective Effect?

Background: Exercise training (ET) has a protective effect on the progression of heart failure, however, the specific mechanism has not been fully explored. Myeloid-derived suppressor cells (MDSCs) are a group of myeloid-derived immunosuppressive cells, which showed a protective effect in the progression of heart failure. Thus, we hypothesized that the protective effect of ET on heart failure may be related to the infiltration of MDSCs. Methods: C57BL/6 mice were made to run on a treadmill 6× a week for 4 weeks followed by isoproterenol injection from third week. Heart function was evaluated by echocardiography and the proportion of MDSCs was detected by flow cytometry. Hypertrophic markers, cardiac fibrosis, and inflammatory factors were detected by real-time PCR, ELISA, histological staining, and Western blot. Results: ET treatment in isoproterenol-induced heart failure mice (n=7) enhanced cardiac function (57% increase in FS%, P =0.002) and improved morphological changes compared with isoproterenol mice (n=17). ET further caused 79% increasing in cardiac MDSCs in isoproterenol mice ( P <0.001). In addition, depletion of MDSCs by 5-Fluorouracil blunted the cardio-protective effect of ET. T-cell proliferation assay showed that ET did not affect the suppressive activity of MDSCs. Furthermore, we found that ET activated the secretion of IL (interleukin)-10 by macrophages in isoproterenol mice. MDSCs expansion and cardio protection was not present in tamoxifen-inducible macrophage-specific IL-10 knockout mice. Western blot results confirmed that IL-10 regulated the differentiation of MDSCs through the translocation of p-STAT3 (signal transducer and activator of transcription 3)/S100A9 (S100 calcium-binding protein A9) to the nucleus. Conclusions: ET could increase MDSCs by stimulating the secretion of IL-10 from macrophage, which was through IL-10/STAT3/S100A9 signaling pathway, thereby achieving the role of heart protection.

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Ameliorating effects of lifelong physical activity on healthy aging and mitochondrial function in human white adipose tissue

The Journals of Gerontology Series A ◽

10.1093/gerona/glab356 ◽

2021 ◽

Author(s):

Anders Gudiksen ◽

Albina Qoqaj ◽

Stine Ringholm ◽

Jørgen Wojtaszewski ◽

Peter Plomgaard ◽

...

Keyword(s):

Adipose Tissue ◽

Exercise Training ◽

White Adipose Tissue ◽

Mitochondrial Function ◽

Mitochondrial Respiration ◽

Healthy Aging ◽

Venous Blood ◽

Oxidative Capacity ◽

Low Grade ◽

Lifelong Exercise

Abstract Growing old is patently among the most prominent risk factors for lifestyle related diseases and deterioration in physical performance. Aging in particular affects mitochondrial homeostasis and maintaining a well-functioning mitochondrial pool is imperative in order to avoid age-associated metabolic decline. White adipose tissue (WAT) is a key organ in energy balance and impaired mitochondrial function in adipocytes has been associated with increased low-grade inflammation, altered metabolism, excessive ROS production and an accelerated aging phenotype. Exercise training improves mitochondrial health but whether lifelong exercise training can sufficiently maintain WAT mitochondrial function is currently unknown. Therefore, to dissect the role and dose-dependence of lifelong exercise training on aging WAT metabolic parameters and mitochondrial function, young and older untrained, as well as moderately and highly exercise trained older male subjects were recruited and abdominal subcutaneous (s)WAT biopsies and venous blood samples were obtained to measure mitochondrial function and key metabolic factors in WAT and plasma. Mitochondrial intrinsic respiratory capacity was lower in sWAT from older than in young subjects. In spite of this, maximal mitochondrial respiration per wet weight, markers of oxidative capacity, and mitophagic capacity were increased in sWAT from lifelong highly exercise trained than all other groups. Furthermore, ROS emission was generally lower in sWAT from lifelong highly exercise trained than older untrained subjects. Taken together, aging reduces intrinsic mitochondrial respiration in human sWAT, but lifelong high volume exercise training increases oxidative capacity by increasing mitochondrial volume likely contributing to healthy aging.

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