UNASSIGNED: Prefrontal cortex (PFC) hemodynamics are regulated by numerous underlying neurophysiological components over multiple temporal scales. The pattern of output signals, such as functional near-infrared spectroscopy fluctuations (i.e., fNIRS), is thus complex. We demonstrate first-of-its-kind evidence that this fNIRS complexity is a marker that captures the influence of endurance capacity and the effects of hydrogen gas (H2) on PFC regulation.
UNASSIGNED: We aim to explore the effects of different physical loads of exercise as well as the intaking of hydrogen gas on the fNIRS complexity of the PFC.
UNASSIGNED: Twenty-four healthy young men completed endurance cycling exercise from 0 (i.e., baseline) to 100% of their physical loads after intaking 20 min of either H2 or placebo gas (i.e., control) on each of two separate visits. The fNIRS measuring the PFC hemodynamics and heart rate (HR) was continuously recorded throughout the exercise. The fNIRS complexity was quantified using multiscale entropy.
UNASSIGNED: The fNIRS complexity was significantly greater in the conditions from 25% to 100% of the physical load (p<0.0005) compared with the baseline and after intaking H2 before exercise; this increase of fNIRS complexity was significantly greater compared with the control (p=0.001∼0.01). At the baseline, participants with a greater fNIRS complexity had a lower HR (β=-0.35∼-0.33, p=0.008∼0.02). Those with a greater increase of complexity had a lower increase of the HR (β=-0.30∼-0.28, p=0.001∼0.002) during exercise.
UNASSIGNED: These observations suggest that fNIRS complexity would be a marker that captures the adaptive capacity of PFC to endurance exercise and to the effects of interventions on PFC hemodynamics.

Dityrosine (Dityr) has been detected in commercial food as a product of protein oxidation and has been shown to pose a threat to human health. This study aims to investigate whether Dityr causes a decrease in lactic acid metabolism in the gastrocnemius muscle during endurance exercise. C57BL/6 mice were administered Dityr or saline by gavage for 13 weeks and underwent an endurance exercise test on a treadmill. Dityr caused a severe reduction in motion displacement and endurance time, along with a significant increase in lactic acid accumulation in the blood and gastrocnemius muscle in mice after exercise. Dityr induced significant mitochondrial defects in the gastrocnemius muscle of mice. Additionally, Dityr induced serious oxidative stress in the gastrocnemius muscle, accompanied by inflammation, which might be one of the causes of mitochondrial dysfunction. Moreover, significant apoptosis in the gastrocnemius muscle increased after exposure to Dityr. This study confirmed that Dityr induced oxidative stress in the gastrocnemius muscle, which further caused significant mitochondrial damage in the gastrocnemius muscle cell, resulting in decreased capacity of lactic acid metabolism and finally affected performance in endurance exercise. This may be one of the possible mechanisms by which highly oxidized foods cause a decreased muscle energy metabolism.

Doxorubicin-induced cardiotoxicity (DIC) adversely impacts patients\' long-term health and quality of life. Its underlying mechanism is complex, involving regulatory cell death mechanisms, such as ferroptosis and autophagy. Moreover, it is a challenge faced by patients undergoing cardiac rehabilitation. Endurance exercise (E-Exe) preconditioning effectively counters DIC injury, potentially through the adenosine monophosphate-activated protein kinase (AMPK) pathway. However, detailed studies on this process\'s mechanisms are scarce. Here, E-Exe preconditioning and DIC models were established using mice and primary cultured adult mouse cardiomyocytes (PAMCs). Akin to ferrostatin-1 (ferroptosis inhibitor), rapamycin (autophagic inducer), and MitoTEMPO (mitochondrial free-radical scavenger), E-Exe preconditioning effectively alleviated Fe2+ accumulation and oxidative stress and improved energy metabolism and mitochondrial dysfunction in DIC injury, as demonstrated by multifunctional, enzymatic, and morphological indices. However, erastin (ferroptosis inducer), 3-methyladenine (autophagic inhibitor), adenovirus-mediated AMPKα2 downregulation, and AMPKα2 inhibition by compound C significantly diminished these effects, both in vivo and in vitro. The results suggest a non-traditional mechanism where E-Exe preconditioning, under mild mitochondrial reactive oxygen species generation, upregulates and phosphorylates AMPKα2, thereby enhancing mitochondrial complex I activity, activating adaptive autophagy, and improving myocardial tolerance to DIC injury. Overall, this study highlighted the pivotal role of mitochondria in myocardial DIC-induced ferroptosis and shows how E-Exe preconditioning activated AMPKα2 against myocardial DIC injury. This suggests that E-Exe preconditioning could be a viable strategy for patients undergoing cardiac rehabilitation.

Diastolic dysfunction is a major cardiac dysfunction, and an important predisposing factor is age. Although exercise training is often used for the prevention and treatment of cardiovascular disease nowadays, little is currently known about whether exercise interventions associated with the slowing of cardiac aging are related to mtp-related pathways. In the present study, the UAS/Tub-Gal4 system was used to knockdown whole-body mtp expression levels in Drosophila, which underwent 2 weeks of endurance training. By conducting different assays and quantifying different indicators, we sought to investigate the relationship between mtp, exercise, and age-related diastolic dysfunction. We found that (1) Drosophila in the mtpRNAi youth group exhibited age-related diastolic dysfunction and had a significantly shorter mean lifespan. (2) Endurance exercise could improve diastolic dysfunction and prolong lifespan in aged Drosophila. (3) Endurance exercise could increase the expression levels of apolpp and Acox3, and decrease the levels of TC, LDL-C, and TG in the aged group. In summary, aging causes age-associated diastolic dysfunction in Drosophila, and systemic knockdown of mtp causes premature age-associated diastolic dysfunction in young Drosophila. Besides, endurance exercise improves age-related diastolic dysfunction and prolongs lifespan.

Atg2 is a key gene in autophagy formation and plays an important role in regulating aging progress. Exercise is an important tool to resist oxidative stress in cells and delay muscle aging. However, the relationship between exercise and the muscle Atg2 gene in regulating skeletal muscle aging remains unclear. Here, overexpression or knockdown of muscle Atg2 gene was achieved by constructing the AtgUAS/MhcGal4 system in Drosophila, and these flies were also subjected to an exercise intervention for 2 weeks. The results showed that both overexpression of Atg2 and exercise significantly increased the climbing speed, climbing endurance, cardiac function, and lifespan of aging flies. They also significantly up-regulated the expression of muscle Atg2, AMPK, Sirt1, and PGC-1α genes, and they significantly reduced muscle malondialdehyde and triglyceride. These positive benefits were even more pronounced when the two were combined. However, the effects of Atg2 knockdown on skeletal muscle, heart, and lifespan were reversed compared to its overexpression. Importantly, exercise ameliorated age-related changes induced by Atg2 knockdown. Therefore, current results confirmed that both overexpression of muscle Atg2 and exercise delayed age-related deteriorations of skeletal muscle, the heart function, and lifespan, and exercise could also reverse age-related changes induced by Atg2 knockdown. The molecular mechanism is related to the overexpression of the Atg2 gene and exercise, which increase the activity of the AMPK/Sirt1/PGC-1α pathway, oxidation and antioxidant balance, and lipid metabolism in aging muscle.

Skeletal muscle consists of different muscle fiber types whose heterogeneity is characterized by different metabolic patterns and expression of MyHC isomers. The transformation of muscle fiber types is regulated by a complex molecular network in which long noncoding (lnc) RNAs play an important role. In this study, we found that lnc-H19 is more enriched in slow muscle fibers. In vitro, interference of lnc-H19 by siRNA significantly promoted the expression of fast muscle fiber gene MyHC IIB and inhibited the expression of the slow muscle fiber gene MyHC I, thereby leading to a fast muscle fiber phenotype. In addition, interference of lnc-H19 significantly inhibited mRNA expression of the mitochondrial genes, such as COX5A, COX-2, UQCRFSL, FABP3, and CD36. Overexpression of lnc-H19 resulted in an opposite result. In vivo, knockdown of lnc-H19 by AAV-shRNA-H19 suppressed the mRNA expression of the slow muscle fiber gene MyHC I and the protein expression of slow-MyHC. Simultaneously, mitochondria were reduced in number, swollen, and vacuolated. The activities of succinate dehydrogenase, lactic dehydrogenase, and superoxide dismutase were significantly inhibited, and malondialdehyde content was significantly increased, indicating that deficiency of lnc-H19 leads to decreased oxidative metabolism and antioxidant capacity in muscle. Furthermore, inhibition of lnc-H19 decreased the weight-bearing swimming time and limb suspension time of mice. In conclusion, our results revealed the role of lnc-H19 in maintaining slow muscle fiber types and maintaining exercise endurance, which may help to further improve the regulatory network of lnc-H19 in muscle function.

Fgf21 has been identified as playing a regulatory role in muscle growth and function. Although the mechanisms through which endurance training regulates skeletal muscle have been widely studied, the contribution of Fgf21 remains poorly understood. Here, muscle size and function were measured, and markers of fiber type were evaluated using immunohistochemistry, immunoblots, or qPCR in endurance-exercise-trained wild-type and Fgf21 KO mice. We also investigated Fgf21-induced fiber conversion in C2C12 cells, which were incubated with lentivirus and/or pathway inhibitors. We found that endurance exercise training enhanced the Fgf21 levels of liver and GAS muscle and exercise capacity and decreased the distribution of skeletal muscle fiber size, and fast-twitch fibers were observed converting to slow-twitch fibers in the GAS muscle of mice. Fgf21 promoted the markers of fiber-type transition and eMyHC-positive myotubes by inhibiting the TGF-β1 signaling axis and activating the p38 MAPK signaling pathway without apparent crosstalk. Our findings suggest that the transformation and function of skeletal muscle fiber types in response to endurance training could be mediated by Fgf21 and its downstream signaling pathways. Our results illuminate the mechanisms of Fgf21 in endurance-exercise-induced fiber-type conversion and suggest a potential use of Fgf21 in improving muscle health and combating fatigue.

The mitochondrial unfolded protein response (UPRmt) and mitophagy are two mitochondrial quality control (MQC) systems that work at the molecular and organelle levels, respectively, to maintain mitochondrial homeostasis. Under stress conditions, these two processes are simultaneously activated and compensate for each other when one process is insufficient, indicating mechanistic coordination between the UPRmt and mitophagy that is likely controlled by common upstream signals. This review focuses on the molecular signals regulating this coordination and presents evidence showing that this coordination mechanism is impaired during aging and promoted by exercise. Furthermore, the bidirectional regulation of reactive oxygen species (ROS) and AMPK in modulating this mechanism is discussed. The hierarchical surveillance network of MQC can be targeted by exercise-derived ROS to attenuate aging, which offers a molecular basis for potential therapeutic interventions for sarcopenia.

We aimed to investigate the impact of a single bout of endurance exercise on the brain-derived neurotrophic factor (BDNF) in humans and analyze how a single bout of endurance exercise impacts the peripheral BDNF types by age group. We performed a systematic literature review by searching PubMed, Elsevier, and Web of Science for studies that included a single bout of endurance exercise in the experimental group and other exercise types in the control group. Eight interventions were included in the study. Overall, a single bout of endurance exercise significantly increased BDNF expression (SMD = 0.30; 95% CI = [0.08, 0.52]; p = 0.001), which was confirmed in the serum BDNF (SMD = 0.30; 95% CI = [0.04, 0.55]; p < 0.001). A non-significant trend was observed in the plasma BDNF (SMD = 0.31; 95% CI = [−0.13, 0.76]; p = 0.017). The serum and plasma BDNF levels significantly increased regardless of age (SMD = 0.35; 95% CI = [0.11, 0.58]; p = 0.004; I2 = 0%). In conclusion, a single bout of endurance exercise significantly elevates BDNF levels in humans without neurological disorders, regardless of age. The serum BDNF is a more sensitive index than the plasma BDNF in evaluating the impact of a single bout of endurance exercise on the BDNF.

UNASSIGNED: The purpose of this study is to explore the effect of carbohydrate only or carbohydrate plus protein supplementation on endurance capacity and muscle damage.
UNASSIGNED: Ten recreationally active male runners (VO2max: 53.61 ± 3.86 ml/kg·min) completed run-to-exhaustion test three times with different intakes of intervention drinks. There was a 7-day wash-out period between tests. Each test started with 60 minutes of running at 70% VO2max (phase 1), followed by an endurance capacity test: time-to-exhaustion running at 80% VO2max (phase 2). Participants randomly ingested either 1) 0.4 g/kg BM carbohydrate before phase 1 and before phase 2 (CHO+CHO), 2) 0.4 g/kg BM protein before phase 1 and 0.4 g/kg BM carbohydrate before phase 2 (PRO+CHO), or 3) 0.4 g/kg BM carbohydrate before phase 1 and 0.4 g/kg BM protein before phase 2 (CHO+PRO). All subjects ingested carbohydrate (CHO) 1.2 g/kg BM during phase 1, and blood samples were obtained before, immediately, and 24 h after exercise for measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and myoglobin (MB).
UNASSIGNED: There was no significant difference in time to exhaustion between the three supplement strategies (CHO+CHO: 432 ± 225 s; PRO+CHO: 463 ± 227 s; CHO+PRO: 461 ± 248 s). However, ALT and AST were significantly lower in PRO+CHO than in CHO+CHO 24 h after exercise (ALT: 16.80 ± 6.31 vs. 24.39 ± 2.54 U/L; AST: 24.06 ± 4.77 vs. 31.51 ± 7.53 U/L, p < 0.05). MB was significantly lower in PRO+CHO and CHO+PRO than in CHO+CHO 24 h after exercise (40.7 ± 15.2; 38.1 ± 14.3; 64.3 ± 28.9 ng/mL, respectively, p < 0.05). CK increased less in PRO+CHO compared to CHO+CHO 24 h after exercise (404.22 ± 75.31 VS. 642.33 ± 68.57 U/L, p < 0.05).
UNASSIGNED: Carbohydrate and protein supplement strategies can reduce muscle damage caused by endurance exercise, but they do not improve endurance exercise capacity.