Effects of aerobic training on markers of autophagy in the elderly

Abstract

Autophagy is a molecular process essential for the maintenance of cellular homeostasis, which appears to (i) decline with age and (ii) respond to physical exercise. In addition, recent evidence suggests a crosstalk between autophagy and toll-like receptor (TLR)-associated inflammatory responses. This study assessed the effects of aerobic exercise training on autophagy and TLR signaling in older subjects. Twentynine healthy women and men (age, 69.7 ± 1.0 year) were randomized to a training (TG) or a control (CG) group. TG performed an 8-week aerobic training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and protein levels of protein 1 light chain 3 (LC3), sequestosome 1 (p62/SQSTM1), beclin-1, phosphorylated unc-51-like kinase (ULK-1), ubiquitin-like autophagy-related (Atg)12, Atg16, and lysosome-associated membrane protein (LAMP)-2 were measured. TLR2 and TLR4 signaling pathways were also analyzed. Peak oxygen uptake increased in TG after the intervention. Protein expression of beclin-1, Atg12, Atg16, and the LC3II/I ratio increased following the training program (p < 0.05), while expression of p62/SQSTM1 and phosphorylation of ULK-1 at Ser 757 were lower (p < 0.05). Protein content of TLR2, TLR4, myeloid differentiation primary response gen 88 (MyD88), and TIR domaincontaining adaptor-inducing interferon (TRIF) were not significantly modified by exercise. The current data indicate that aerobic exercise training induces alterations in multiple markers of autophagy, which seem to be unrelated to changes in TLR2 and TLR4 signaling pathways. These results expand knowledge on exerciseinduced autophagy adaptations in humans and suggest that the exercise type employed may be a key factor explaining the potential relationship between autophagy and TLR pathways.

Mitochondria Initiate and Regulate Sarcopenia

“…Exercise-induced Pink1 activation of Drp1 (112) could also target dysfunctional mitochondria for mitophagy. This idea is supported by recent data from Mejias-Pena et al (92) who found an increase in the protein abundance of autophagy proteins Beclin-1, Atg12, Atg16, and the LC3II/I ratio in blood mononuclear cells of elderly subjects after 8 weeks of aerobic exercise. Furthermore, 8 weeks of aerobic exercise has been reported to increase autophagy proteins Beclin-1, ATG7, and MuRF-1 in muscles of old mice (70).…”

Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity

“…; Mejías‐Peña et al . ; Kim & Hood, ). He and colleagues () observed a decreased association of Beclin 1 with Bcl‐2 within 30 min of acute exercise, despite a rise in total protein levels of Beclin 1.…”

“…We also observed an increase in Beclin 1 protein expression in young muscle exposed to CCA. Previous reports have identified an increase in Beclin 1 following both acute and chronic exercise (He et al 2012;Ju et al 2016), but some opposing results have also been documented (McMillan et al 2015;Mejías-Peña et al 2016;Kim & Hood, 2017). He and colleagues (2012) observed a decreased association of Beclin 1 with Bcl-2 within 30 min of acute exercise, despite a rise in total protein levels of Beclin 1.…”

Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects

“…On one hand, autophagy negatively regulates inflammation by inducing changes on the TLR-mediated inflammatory response, as we recently showed [9]. On the other hand, autophagy may function as a negative counter-regulatory mechanism for inflammasome activation, thus providing a checkpoint to limit the development of inflammation [36].…”