Correction: Lifelong aerobic exercise protects against inflammaging and cancer.
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ABSTRACT:
SUBMITTER: Nilsson MI
PROVIDER: S-EPMC7219773 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Correction: Lifelong aerobic exercise protects against inflammaging and cancer.
Nilsson Mats I MI Bourgeois Jacqueline M JM Nederveen Joshua P JP Leite Marlon R MR Hettinga Bart P BP Bujak Adam L AL May Linda L Lin Ethan E Crozier Michael M Rusiecki Daniel R DR Moffatt Chris C Azzopardi Paul P Young Jacob J Yang Yifan Y Nguyen Jenny J Adler Ethan E Lan Lucy L Tarnopolsky Mark A MA
PloS one 20200513 5
[This corrects the article DOI: 10.1371/journal.pone.0210863.]. ...[more]
Similar Datasets
Project description:Biological aging is associated with progressive damage accumulation, loss of organ reserves, and systemic inflammation ('inflammaging'), which predispose for a wide spectrum of chronic diseases, including several types of cancer. In contrast, aerobic exercise training (AET) reduces inflammation, lowers all-cause mortality, and enhances both health and lifespan. In this study, we examined the benefits of early-onset, lifelong AET on predictors of health, inflammation, and cancer incidence in a naturally aging mouse model (C57BL/J6). Lifelong, voluntary wheel-running (O-AET; 26-month-old) prevented age-related declines in aerobic fitness and motor coordination vs. age-matched, sedentary controls (O-SED). AET also provided partial protection against sarcopenia, dynapenia, testicular atrophy, and overall organ pathology, hence augmenting the 'physiologic reserve' of lifelong runners. Systemic inflammation, as evidenced by a chronic elevation in 17 of 18 pro- and anti-inflammatory cytokines and chemokines (P < 0.05 O-SED vs. 2-month-old Y-CON), was potently mitigated by lifelong AET (P < 0.05 O-AET vs. O-SED), including master regulators of the cytokine cascade and cancer progression (IL-1β, TNF-α, and IL-6). In addition, circulating SPARC, previously known to be upregulated in metabolic disease, was elevated in old, sedentary mice, but was normalized to young control levels in lifelong runners. Remarkably, malignant tumours were also completely absent in the O-AET group, whereas they were present in the brain (pituitary), liver, spleen, and intestines of sedentary mice. Collectively, our results indicate that early-onset, lifelong running dampens inflammaging, protects against multiple cancer types, and extends healthspan of naturally-aged mice.
| S-EPMC6347267 | biostudies-literature
Project description:Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice. In addition, we analysed inflammatory response in the kidney of aged CalpTG and wild-type mice, and in both in vivo (monosodium urate peritonitis) and in vitro models of inflammation. At two years, CalpTG mice had preserved kidney tissue, less vascular remodelling and less markers of senescence than wild-type mice. Nevertheless, CalpTG mice lifespan was not extended, due to the development of lethal spleen tumors. Inflammatory pathways were less expressed in aged CalpTG mice, especially cytokines related to NF-κB and NLRP3 inflammasome activation. CalpTG mice had reduced macrophage infiltration with aging and CalpTG mice produced less IL-1α and IL-1β in vivo in response to inflammasome activators. In vitro, macrophages from CalpTG mice produced less IL-1α in response to particulate activators of inflammasome. Calpains inhibition protects against inflammaging, limiting kidney and vascular lesions related to aging.
| S-EPMC5556007 | biostudies-other
Project description:Age-associated chronic basal inflammation compromises muscle mass and adaptability, but exercise training may exert an anti-inflammatory effect. This investigation assessed basal and exercise-induced inflammation in three cohorts of men: young exercisers [YE; n = 10 men; 25 ± 1 yr; maximal oxygen consumption (V̇o2max), 53 ± 3 mL·kg-1·min-1; quadriceps area, 78 ± 3 cm2; means ± SE], old healthy nonexercisers (OH; n = 10; 75 ± 1 yr; V̇o2max, 22 ± 1 mL·kg-1·min-1; quadriceps area, 56 ± 3 cm2), and lifelong exercisers with an aerobic training history of 53 ± 1 yr (LLE; n = 21; 74 ± 1 yr; V̇o2max, 34 ± 1 mL·kg-1·min-1; quadriceps area, 67 ± 2 cm2). Resting serum IL-6, TNF-α, C-reactive protein, and IGF-1 levels were measured. Vastus lateralis muscle biopsies were obtained at rest (basal) and 4 h after an acute exercise challenge (3 × 10 repetitions, 70% 1-repetition maximum) to assess gene expression of cytokines [IL-6, TNF-α, IL-1β, IL-10, IL-4, interleukin-1 receptor antagonist (IL-1Ra), and transforming growth factor-β (TGF-β)], chemokines [IL-8 and monocyte chemoattractant protein-1 (MCP-1)], cyclooxygenase enzymes [cyclooxygenase-1 and -2 (COX-1 and COX-2, respectively), prostaglandin E2 synthases [microsomal prostaglandin E synthase 1 (mPGES-1) and cytosolic prostaglandin E2 synthase (cPGES)] and receptors [prostaglandin E2 receptor EP3 and EP4 subtypes (EP3 and EP4, respectively), and macrophage markers [cluster of differentiation 16b (CD16b) and CD163], as well as basal macrophage abundance (CD68+ cells). Aging led to higher (P ≤ 0.05) circulating IL-6 and skeletal muscle COX-1, mPGES-1, and CD163 expression. However, LLE had significantly lower serum IL-6 levels (P ≤ 0.05 vs. OH) and a predominantly anti-inflammatory muscle profile [higher IL-10 (P ≤ 0.05 vs. YE), TNF-α, TGF-β, and EP4 levels (P ≤ 0.05 vs. OH)]. In OH only, acute exercise increased expression of proinflammatory factors TNF-α, TGF-β, and IL-8 (P ≤ 0.05). LLE had postexercise gene expression similar to YE, except lower IL-10 (P ≤ 0.10), mPGES-1, and EP3 expression (P ≤ 0.05). Thus, although aging led to a proinflammatory profile within blood and muscle, lifelong exercise partially prevented this and generally preserved the acute inflammatory response to exercise seen in young exercising men. Lifelong exercise may positively impact muscle health throughout aging by promoting anti-inflammation in skeletal muscle.NEW & NOTEWORTHY This study assessed a unique population of lifelong aerobic exercising men and demonstrated that their activity status exerts an anti-inflammatory effect in skeletal muscle and circulation. Furthermore, we provide evidence that the inflammatory response to acute exercise is dysregulated by aging but preserved with lifelong exercise, which might improve skeletal muscle resilience to unaccustomed loading and adaptability into late life.
| S-EPMC6985808 | biostudies-literature
Project description:To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF). Isoproterenol was injected into rats to create CHF models. The rats were then subsequently divided into saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Compared to the CHF group, the canagliflozin combined with the aerobic exercise group had superior ventricular remodeling and cardiac function. In rats treated with canagliflozin combined with aerobic exercise, the expression of cytochrome P450 (CYP) 4A3, CYP4A8, COL1A1, COL3A1, and FN1 was reduced, while the expression of CYP26B1, ALDH1A2, and CYP1A1 increased significantly. Additionally, canagliflozin combined with aerobic exercise decreased the phosphorylation of AKT and ERK1/2. Canagliflozin combined with aerobic exercise has a positive effect on the development of CHF via the regulation of retinol metabolism and the AKT/ERK signaling pathway.
| S-EPMC10910240 | biostudies-literature
Project description:Low muscle mass and frailty are especially prevalent in older women and may be accelerated by age-related inflammation. Habitual physical activity throughout the life span (lifelong exercise) may prevent muscle inflammation and associated pathologies, but this is unexplored in women. This investigation assessed basal and acute exercise-induced inflammation in three cohorts of women: young exercisers (YE, n = 10, 25 ± 1 yr, [Formula: see text]: 44 ± 2 mL/kg/min, quadriceps size: 59 ± 2 cm2), old healthy nonexercisers (OH, n = 10, 75 ± 1 yr, [Formula: see text]: 18 ± 1 mL/kg/min, quadriceps size: 40 ± 1 cm2), and lifelong aerobic exercisers with a 48 ± 2 yr aerobic training history (LLE, n = 7, 72 ± 2 yr, [Formula: see text]: 26 ± 2 mL/kg/min, quadriceps size: 42 ± 2 cm2). Resting serum IL-6, TNF-α, C-reactive protein (CRP), and IGF-1 were measured. Vastus lateralis muscle biopsies were obtained at rest (basal) and 4 h after an acute exercise challenge (3 × 10 reps, 70% 1-repetition maximum) to assess gene expression of cytokines (IL-6, TNF-α, IL-1β, IL-10, IL-4, IL-1Ra, TGF-β), chemokines (IL-8, MCP-1), cyclooxygenase enzymes (COX-1, COX-2), prostaglandin E2 synthases (mPGES-1, cPGES) and receptors (EP3-4), and macrophage markers (CD16b, CD163), as well as basal macrophage abundance (CD68+ cells). The older cohorts (LLE + OH combined) demonstrated higher muscle IL-6 and COX-1 (P ≤ 0.05) than YE, whereas LLE expressed lower muscle IL-1β (P ≤ 0.05 vs. OH). Acute exercise increased muscle IL-6 expression in YE only, whereas the older cohorts combined had the higher postexercise expression of IL-8 and TNF-α (P ≤ 0.05 vs. YE). Only LLE had increased postexercise expression of muscle IL-1β and MCP-1 (P ≤ 0.05 vs. preexercise). Thus, aging in women led to mild basal and exercise-induced inflammation that was unaffected by lifelong aerobic exercise, which may have implications for long-term function and adaptability.NEW & NOTEWORTHY We previously reported a positive effect of lifelong exercise on skeletal muscle inflammation in aging men. This parallel investigation in women revealed that lifelong exercise did not protect against age-related increases in circulating or muscle inflammation and that preparedness to handle loading stress was not preserved by lifelong exercise. Further investigation is necessary to understand why lifelong aerobic exercise may not confer the same anti-inflammatory benefits in women as it does in men.
| S-EPMC7792846 | biostudies-literature
Project description:Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson's trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR59230A. Our study suggested that aerobic exercise training could improve cardiac systolic function and alleviate LV chamber dilation, cardiac fibrosis and hypertrophy in HF mice. The mechanism responsible for the protective effects of aerobic exercise is associated with the activation of the β3-AR-nNOS-NO pathway.
| S-EPMC5473571 | biostudies-literature
Project description:The purpose of this investigation was to evaluate the effects of aging and lifelong exercise on skeletal muscle components of the innate immune system. Additionally, the effects of an acute resistance exercise (RE) challenge were explored. Three groups of men were studied: young exercisers (YE: n = 10, 25 ± 1 yr; V̇o2max: 53 ± 3 mL/kg/min; quadriceps size: 78 ± 3 cm2), lifelong aerobic exercisers with a 53 ± 1 yr training history (LLE; n = 21, 74 ± 1 yr; V̇o2max: 34 ± 1 mL/kg/min; quadriceps size: 67 ± 2 cm2), and old healthy nonexercisers (OH: n = 10, 75 ± 1 yr; V̇o2max: 22 ± 1 mL/kg/min, quadriceps size: 56 ± 3 cm2). Vastus lateralis muscle biopsies were obtained in the basal state and 4 h after RE (3 × 10 reps, 70% of 1 repetition maximum) to assess Toll-like receptors (TLR)1-10, TLR adaptors (Myd88 and TRIF), and NF-κB pathway components (IκΒα and IKKβ) mRNA expression. Basal TLR3, TLR6, and TLR7 tended to be higher (P ≤ 0.10) with aging (LLE and OH combined). In general, RE increased expression of TLR1 and TLR8 (P ≤ 0.10) and TLR3 and TLR4 (P < 0.05), although TLR3 did not respond in OH. Both TLR adaptors also responded to the exercise bout; these were primarily (Myd88, main effect P ≤ 0.10) or exclusively (TRIF, P < 0.05) driven by the OH group. In summary, aging appears to increase basal expression of some innate immune components in human skeletal muscle, and lifelong aerobic exercise does not affect this age-related increase. An exercise challenge stimulates the expression of several TLRs, while the TLR adaptor response appears to be dysregulated with aging and maintained with lifelong exercise. Partially preserved muscle mass, coupled with a notable immunity profile, suggests lifelong exercisers are likely better prepared for a stress that challenges the immune system.NEW & NOTEWORTHY Findings from this investigation provide novel insight into the effect of aging and lifelong aerobic exercise on structural components of the innate immune system in skeletal muscle of humans. Data presented here suggest aging increases basal expression of select Toll-like receptors (TLRs), and lifelong exercise does not impact this age-related increase. Additionally, acute exercise stimulates gene expression of several TLRs, while the adaptor response is likely dysregulated with aging and maintained with lifelong exercise.
| S-EPMC7792837 | biostudies-literature
Project description:To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF).During 10 days, isoproterenol (5 mg/kg/d) was injected into rats to create CHF models. The rats were then randomized into four groups and administered with saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Then, we performed gene expression profiling using the data obtained by RNA-seq in the Control, HF, LC and LC-AE groups.
2023-02-17 | GSE225149 | GEO
Project description:Key pointsThe results of the present study establish the temporal pattern of age-related vascular dysfunction across the adult lifespan in sedentary mice consuming a non-Western diet, and the underlying mechanisms The results demonstrate that consuming a Western diet accelerates and exacerbates vascular ageing across the lifespan in sedentary mice They also show that lifelong voluntary aerobic exercise has remarkable protective effects on vascular function throughout the lifespan, in the setting of ageing alone, as well as ageing compounded by Western diet consumption Overall, the results indicate that amelioration of mitochondrial oxidative stress and inflammation are key mechanisms underlying the voluntary aerobic exercise-associated preservation of vascular function across the lifespan in both the presence and absence of a Western dietary pattern ABSTRACT: Advancing age is the major risk factor for cardiovascular diseases, driven largely by vascular endothelial dysfunction (impaired endothelium-dependent dilatation, EDD) and aortic stiffening (increased aortic pulse wave velocity, aPWV). In humans, vascular ageing occurs in the presence of differences in diet and physical activity, but the interactive effects of these factors are unknown. We assessed carotid artery EDD and aPWV across the lifespan in mice consuming standard (normal) low-fat chow (NC) or a high-fat/high-sucrose Western diet (WD) in the absence (sedentary, SED) or presence (voluntary wheel running, VWR) of aerobic exercise. Ageing impaired nitric oxide-mediated EDD (peak EDD 88 ± 12% 6 months P = 0.003 vs. 59 ± 9% 27 months NC-SED), which was accelerated by WD (60 ± 18% 6 months WD-SED). In NC mice, aPWV increased 32% with age (423 ± 13 cm/s at 24 months P < 0.001 vs. 321 ± 12 cm/s at 6 months) and absolute values were an additional ∼10% higher at any age in WD mice (P = 0.042 vs. NC-SED). Increases in aPWV with age in NC and WD mice were associated with 30-65% increases in aortic intrinsic wall stiffness (6 vs. 19-27 months, P = 0.007). Lifelong aerobic exercise prevented age- and WD-related vascular dysfunction across the lifespan, and this protection appeared to be mediated by mitigation of vascular mitochondrial oxidative stress and inflammation. Our results depict the temporal impairment of vascular function over the lifespan in mice, acceleration and exacerbation of that dysfunction with WD consumption, the remarkable protective effects of voluntary aerobic exercise, and the underlying mechanisms.
| S-EPMC7856030 | biostudies-literature
Project description:When quantum computing becomes a wide-spread commercial reality, Quantum Search Algorithms (QSA) and especially Grover's QSA will inevitably be one of their main applications, constituting their cornerstone. Most of the literature assumes that the quantum circuits are free from decoherence. Practically, decoherence will remain unavoidable as is the Gaussian noise of classic circuits imposed by the Brownian motion of electrons, hence it may have to be mitigated. In this contribution, we investigate the effect of quantum noise on the performance of QSAs, in terms of their success probability as a function of the database size to be searched, when decoherence is modelled by depolarizing channels' deleterious effects imposed on the quantum gates. Moreover, we employ quantum error correction codes for limiting the effects of quantum noise and for correcting quantum flips. More specifically, we demonstrate that, when we search for a single solution in a database having 4096 entries using Grover's QSA at an aggressive depolarizing probability of 10-3, the success probability of the search is 0.22 when no quantum coding is used, which is improved to 0.96 when Steane's quantum error correction code is employed. Finally, apart from Steane's code, the employment of Quantum Bose-Chaudhuri-Hocquenghem (QBCH) codes is also considered.
| S-EPMC5141447 | biostudies-literature