Resistance Exercise Training as a New Trend in Alzheimer's Disease Research: From Molecular Mechanisms to Prevention.

Alzheimer's disease is a pathology characterized by the progressive loss of neuronal connections, which leads to gray matter atrophy in the brain. Alzheimer's disease is the most prevalent type of dementia and has been classified into two types, early onset, which has been associated with genetic factors, and late onset, which has been associated with environmental factors. One of the greatest challenges regarding Alzheimer's disease is the high economic cost involved, which is why the number of studies aimed at prevention and treatment have increased. One possible approach is the use of resistance exercise training, given that it has been shown to have neuroprotective effects associated with Alzheimer's disease, such as increasing cortical and hippocampal volume, improving neuroplasticity, and promoting cognitive function throughout the life cycle. However, how resistance exercise training specifically prevents or ameliorates Alzheimer's disease has not been fully characterized. Therefore, the aim of this review was to identify the molecular basis by which resistance exercise training could prevent or treat Alzheimer's disease.

Time-restricted feeding combined with resistance exercise prevents obesity and improves lipid metabolism in the liver of mice fed a high-fat diet.

Nonalcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat in the liver, is estimated to be the most common liver disease worldwide. Obesity is a major risk factor and contributor, and, accordingly, weight loss can improve NAFLD. Previous studies in preclinical models of diet-induced obesity and fatty liver disease have shown the independent benefits of resistance exercise training (RT) and time-restricted feeding (TRF) in preventing weight gain and hepatic build-up of fat. Here, we tested the combined effect of TRF and RT on obesity and NAFLD in mice fed a high-fat diet. Our results showed that both TRF-8-h food access in the active phase-and RT-consisting of three weekly sessions of ladder climbing-attenuated body weight gain, improved glycemic homeostasis, and decreased the accumulation of lipids in the liver. TRF combined with RT improved the respiratory exchange rate, energy expenditure, and mitochondrial respiration in the liver. Furthermore, gene expression analysis in the liver revealed lower mRNA expression of lipogenesis and inflammation genes along with increased mRNA of fatty acid oxidation genes in the TRF + RT group. Importantly, combined TRF + RT was shown to be more efficient in preventing obesity and metabolic disorders. In conclusion, TRF and RT exert complementary actions compared with isolated interventions, with significant effects on metabolic disorders and NAFLD in mice.NEW & NOTEWORTHY Whether time-restricted feeding (TRF) combined with resistance exercise training (RT) may be more efficient compared with these interventions alone is still unclear. We show that when combined with RT, TRF provided additional benefits, being more effective in increasing energy expenditure, preventing weight gain, and regulating glycemic homeostasis than each intervention alone. Thus, our results demonstrate that TRF and RT have complementary actions on some synergistic pathways that prevented obesity and hepatic liver accumulation.

Combined Exercise Training Promotes More Benefits on Cardiovascular Autonomic Modulation in Ovariectomized Rats Than Isolated Aerobic or Resistance Training.

Introduction: Cardiovascular risk increase after ovarian deprivation has been extensively demonstrated by our research group through cardiovascular autonomic analysis. Interventions involving different types of exercises, such as resistance exercises or combined exercises (aerobic and resistance) have been widely recommended to prevent or minimize neuromuscular decline in postmenopausal women, which is aggravated by a sedentary lifestyle. Experimentally, the cardiovascular effects of resistance or combined training, as well as comparison between aerobic, resistance, and combined training, in ovariectomized animals are scarce. Purpose: In this study, we hypothesized that the combination of aerobic and resistance training may be more effective in preventing muscle mass loss, as well as improving cardiovascular autonomic modulation and baroreflex sensitivity, than aerobic or resistance training individually in ovariectomized rats. Animals and Methods: Female rats were divided into 5 groups: sedentary (C); ovariectomized (Ovx); trained ovariectomized submitted to aerobic training (OvxAT); resistance training (OvxRT); combined training (OvxCT). Exercise training lasted 8 weeks, with the combined group alternating between aerobic training and resistance training every other day. At the end of the study, glycemia and insulin tolerance were evaluated. Arterial pressure (AP) was directly recorded. Baroreflex sensitivity was assessed by heart rate response to changes in arterial pressure. Cardiovascular autonomic modulation was evaluated by spectral analysis. Results: Combined training was the only training regime that increased baroreflex sensitivity for tachycardic response and reduced all systolic blood pressure variability parameters. Furthermore, all animals submitted to exercise training on a treadmill (OvxAT and OvxCT) presented lower systolic, diastolic, and mean pressure, as well as improvements in the autonomic modulation for the heart. Conclusion: Combined training showed to be more effective than isolated aerobic and resistance training, mixing the isolated benefits of each modality. It was the only modality able to increase baroreflex sensitivity to tachycardic responses, reduce arterial pressure and all parameters of vascular sympathetic modulation.

Resistance exercise improves learning and memory and modulates hippocampal metabolomic profile in aged rats.

Physical activity has been considered an important non-medication intervention to preserve mnemonic processes during aging. However, how resistance exercise promotes such benefits remains unclear. A possible hypothesis is that brain-metabolic changes of regions responsible for memory consolidation is affected by muscular training. Therefore, we analyzed the memory, axiety and the metabolomic of aged male Wistar rats (19-20 months old in the 1st day of experiment) submitted to a 12-week resistance exercise protocol (EX, n = 11) or which remained without physical exercise (CTL, n = 13). Barnes maze, elevated plus maze and inhibitory avoidance tests were used to assess the animals' behaviour. The metabolomic profile was identified by nuclear magnetic resonance spectrometry. EX group had better performance in the tests of learning and spatial memory in Barnes maze, and an increase of short and long-term aversive memories formation in inhibitory avoidance. In addition, the exercised animals showed a greater amount of metabolites, such as 4-aminobutyrate, acetate, butyrate, choline, fumarate, glycerol, glycine, histidine, hypoxanthine, isoleucine, leucine, lysine, niacinamide, phenylalanine, succinate, tyrosine, valine and a reduction of ascorbate and aspartate compared to the control animals. These data indicate that the improvement in learning and memory of aged rats submitted to resistance exercise program is associated by changes in the hippocampal metabolomic profile.

Resistance exercise training ameliorates chronic kidney disease outcomes in a 5/6 nephrectomy model.

Chronic kidney disease (CKD) is defined by decreased glomerular filtration rate (GFR) or increased albumin excretion leading to renal injury. However, exercise training is an important non-pharmacological intervention that ameliorates and protects against Diabetes Mellitus, cardiovascular disease, and CKD. AIM: Our aim was to evaluate the capability of resistance exercise training (RET) to improve CKD outcomes and the contribution of the renal and muscular Akt/mTOR signaling pathway for RET beneficial effects on a CKD model. MAIN METHODS: Male Wistar rats were subjected to RET, followed for 10 weeks, and randomly divided into 5 groups: Sham: Sham-operated; sedentary and nephrectomy (5/6Nx) (SNS); exercising post-5/6Nx (SNE); exercising pre-5/6Nx (ENS); exercising pre- and post-5/6Nx (ENE). The systolic blood pressure (BP) was measured. Creatinine, proteinuria, and blood urea nitrogen (BUN) were evaluated. After euthanasia Renal and muscular Akt/mTOR signaling pathways were analyzed. KEY FINDING: Our study showed that the SNS presented renal injury, hypertension, weight and muscular mass loss and a higher mortality rate. SNS group also decreased renal IL-10 and increased TNF-alfa and TGF-Beta. Renal AKT, mTOR, and rpS6 pathway were increased, PTEN was decreased on SNS. And muscular Akt and mTOR were decreased on SNS. SIGNIFICANCE: The RET before and after the 5/6Nx ameliorates all these parameters mentioned above, suggesting that RET is a good non-pharmacological approach to diminish complications frequently found in CKD. We also suggest that the AKT-m-TOR pathway can play an important role in these beneficial outcomes of RET on the CKD animal model.

Effects of resistance exercise training on redox homeostasis in older adults. A systematic review and meta-analysis.

BACKGROUND: Resistance exercise training (RET) has proven effective at reducing the risk of chronic disease in older populations, and it appears to regulate redox homeostasis. AIMS: To determine the effects of RET on redox homeostasis in older people. STUDY DESIGN: A systematic review and meta-analysis of randomized clinical trials identified by searching MEDLINE, Web of Science, EMBASE, Sportdiscus, LILACS, CENTRAL and CINAHL. We included studies of subjects aged 65 years or older, with or without pathologies, and including RET metrics with quantified molecular oxidation and antioxidant capacity outcomes. RESULTS: Fifteen studies were included in this review. Agreement between reviewers reached a kappa value of 0.725. There were a total of 614 participants, with an average age of 68.1 years. Five (for molecular oxidation markers) and three (for antioxidant capacity markers) studies included data that quantified the effects of RET on homeostasis redox. The results of the meta-analysis showed that there were no differences in the molecular oxidation markers (SMD = -0.26; 95% CI = -0.57 to 0.05; P = 0.10; I2 = 0%) and antioxidant capacity markers (SMD = 0.53; 95% CI = -0.20 to 1.26; P = 0.16; I2 = 71.5%) in healthy older people after a RET of 8-24 weeks compared to non-intervention. CONCLUSIONS: Based on a small number of studies of low methodological quality, this systematic review with meta-analysis suggests that RET is not effective at reducing molecular oxidation markers in healthy older people. More research is needed on the effects of RET on redox homeostasis in older people. PROSPERO REGISTRATION NUMBER: CRD42019121529.

Nandrolone decanoate and resistance exercise affect prostate morphology and hormone receptor interface in adult rats with implications for the aging process.

BACKGROUND: Nandrolone decanoate (ND) is an anabolic-androgenic steroid, and its indiscriminate use leads to subclinical alterations in the hypothalamic-pituitary-gonadal axis and androgen-dependent organs. OBJECTIVES: To evaluate the effects of ND, either alone or in combination with resistance exercise (RE), on the levels of sex hormones, converting enzymes, and steroid receptors and the morphology of the ventral prostate (VP) in adult and aged rats. METHODS: Forty Sprague-Dawley adult and aged rats were divided into four groups each, sedentary and trained with and without ND. The groups received treatments over 8 weeks. Adult animals were sacrificed immediately following treatment completion, while the aged groups were left untreated until 300 days of age. RESULTS: Adult and aged animals showed reductions in testosterone levels following the different treatments, and 17ß-estradiol levels were decreased in the ND-treated groups. The level of 5α-reductase type 2 (5αR2) and aromatase was increased significantly in the prostates of adult animals that performed RE. However, aromatase levels were decreased in the prostates of aged animals that performed RE and were treated with ND, while 5αR2 levels were reduced in aged animals that performed RE without ND treatment. When sex receptors levels were examined, the aged and trained animals presented low androgen receptor (AR) levels. Estrogen receptors (ERs) levels were increased in the prostates of adult animals that received ND. ERß levels were reduced after treatments in aged animals. The heights of the prostatic epithelium were reduced in all adult treated animals, coinciding with increases in PCNA and PAR4 levels. DISCUSSION: ND and RE alter the levels of hormone, converting enzymes, and sex steroid receptors and the morphology of the VP. These effects were observed in both adult and aged rats. CONCLUSION: ND, either with or without RE, during post-puberty stage is able to interfere with the morphophysiology of the prostate.