Resistance Training Diminishes the Expression of Exosome CD63 Protein without Modification of Plasma miR-146a-5p and cfDNA in the Elderly

Abstract

Aging-associated inflammation is characterized by senescent cell-mediated secretion of high levels of inflammatory mediators, such as microRNA (miR)-146a. Moreover, a rise of circulating cell-free DNA (cfDNA) is also related to systemic inflammation and frailty in the elderly. Exosome-mediated cell-to-cell communication is fundamental in cellular senescence and aging. The plasma changes in exercise-promoted miR-146a-5p, cfDNA, and exosome release could be the key to facilitate intercellular communication and systemic adaptations to exercise in aging. Thirty-eight elderly subjects (28 trained and 10 controls) volunteered in an 8-week resistance training protocol. The levels of plasma miR-146a-5p, cfDNA, and exosome markers (CD9, CD14, CD63, CD81, Flotillin [Flot]-1, and VDAC1) were measured prior to and following training. Results showed no changes in plasma miR-146a-5p and cfDNA levels with training. The levels of exosome markers (Flot-1, CD9, and CD81) as well as exosome-carried proteins (CD14 and VDAC1) remained unchanged, whereas an attenuated CD63 response was found in the trained group compared to the controls. These findings might partially support the anti-inflammatory effect of resistance training in the elderly as evidenced by the diminishment of exosome CD63 protein expression, without modification of plasma miR-146a-5p and cfDNA.

Three Months of Strength Training Changes the Gene Expression of Inflammation-Related Genes in PBMC of Older Women: A Randomized Controlled Trial

“…Interestingly, many of the affected pathways are related to the Senescence Associated Secretory Profile (SASP), such as TREM1, LXR/RXR, Toll-Like Receptor Signalling, T-cell Exhaustion Signalling, Telomerase Signalling and Th2 pathways. This supports the hypothesis that strength training can affect and/or attenuate SASP, resulting in lower CLIP [52][53][54][55].…”

Exercise Training and Circulating Small Extracellular Vesicles: Appraisal of Methodological Approaches and Current Knowledge

“…To our knowledge, there are currently four reports describing the influence of prior exercise training on preparations of circulating small EVs derived from resting humans (Hou et al, 2019;Nair et al, 2020;Estébanez et al, 2021;Garai et al, 2021; Table 2), three of which separated small EVs from plasma (Hou et al, 2019;Nair et al, 2020;Estébanez et al, 2021) and one which has separated small EVs from serum (Garai et al, 2021). The first study reported 1.8-fold greater abundance of miR-342-5p at rest in preparations of small EVs derived from young (19 to 22 years) male rowers with at least 1 year of training experience compared to sedentary controls (n = 16 in each group).…”

“…Therefore it is unclear whether a greater magnitude of fitness at younger age would create additional or alternative differences in the profile of resting small EVs between either the trained or sedentary group in the aforementioned study (Nair et al, 2020). The third study was in male and female older adults (∼73 years) that compared an 8 week resistance exercise training intervention (n = 28) to a sedentary control group (n = 10; Estébanez et al, 2021). However, the analysis was limited to the presence of small EVs via quantification of total exosome protein, identification of six marker proteins of small EVs via Western blot, and one proposed miRNA cargo of small EVs (miR-146a-5p; Estébanez et al, 2021).…”

“…The third study was in male and female older adults (∼73 years) that compared an 8 week resistance exercise training intervention (n = 28) to a sedentary control group (n = 10; Estébanez et al, 2021). However, the analysis was limited to the presence of small EVs via quantification of total exosome protein, identification of six marker proteins of small EVs via Western blot, and one proposed miRNA cargo of small EVs (miR-146a-5p; Estébanez et al, 2021). Of these, only the small EV marker CD63 exhibited a differential pattern between groups with the increase of ∼7% in the training groups being less than the ∼43% increase in the sedentary control group.…”

“…Much of the current interest regarding the response of EVs to exercise has been focused on a subfraction of EVs in smaller size ranges (diameters of 50-150 nm), termed "small EVs" (Estébanez et al, 2020;Vechetti et al, 2020;Nederveen et al, 2021), with several studies having now investigated the effect of exercise training on the circulating profile (particle number, concentration/abundance, cargo, and/or cargo density) of small EVs (Chaturvedi et al, 2015;Bei et al, 2017;Bertoldi et al, 2018;Ma et al, 2018;Hou et al, 2019;Barcellos et al, 2020;Castaño et al, 2020;Nair et al, 2020;Xiang et al, 2020;Estébanez et al, 2021;Gao et al, 2021).…”